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RSC Medicinal Chemistry

The journal for research and review articles in medicinal chemistry and related drug discovery science

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RSC Medicinal Chemistry  is a Transformative Journal and Plan S compliant

Impact factor: 4.1*

Time to first decision (all decisions): 10.0 days**

Time to first decision (peer reviewed only): 30.0 days***

Editor-in-Chief: Mike Waring

CiteScore: 5.8****

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Meet the team

Journal scope.

RSC Medicinal Chemistry publishes significant research in medicinal chemistry and related drug discovery science.

Research articles published in this journal must show a breakthrough or significant advance on previously published work, or bring new thinking or results that will have a strong impact in their field.

Examples of areas within the journal's scope are:

• Design, synthesis and biological evaluation of novel chemical entities or biotherapeutic modalities. To be suitable for publication these must exhibit significant potential as new pharmacological agents, tools, probes or potential drugs.
• Modifications of known chemical entities or biotherapeutic modalities that result in a significantly greater understanding of their structure-activity relationships, an improvement of their properties or provide other information of significant value, for example, the identification of a new target or mode of action for a known agent. Routine modifications with minimal or no improvement are not suitable for  RSC Medicinal Chemistry .

• Novel methodologies and technologies in the broader chemical and biological sciences (for example, enabling synthetic chemistry, chemical biology, -omics sciences, nanoscience) with application to drug discovery, target identification or elucidation of the mechanism of action. Biological studies should present sufficient innovation with respect to the chemistry.
• Computational studies are welcome where they significantly advance medicinal chemistry knowledge. Studies that use established computational methods should include an original prediction and be accompanied by new experimental data which validates the prediction made. Studies that report novel computational methodology must demonstrate its use in medicinal chemistry through comparison with experimental data. Computational research that does not clearly relate the results obtained to experimental data or that has no demonstrated utility (or where the utility is unlikely to advance the field significantly) is not suitable for RSC Medicinal Chemistry. Docking studies presented without experimental data are not suitable for publication in the journal.
• Studies that examine the effect of the molecular structure of a compound on pharmacokinetic behaviour and pharmacodynamics.
• Studies that present new insights into drug design based on analysis of existing experimental datasets or new theoretical approaches if supported by experimental evidence.
• Studies presenting new drug delivery systems with novel chemical agents are welcomed, in particular those that involve chemical modification of the delivery system of conjugation with novel delivery vectors. Those that focus solely on formulations of known drugs are not suitable for publication in RSC Medicinal Chemistry.

Note that studies where new or existing compounds are tested as pharmacological agents will only be considered if they are carried out in the presence of clear positive and negative controls. Studies of this type should include a clearly defined and hypothesis-driven compound design rationale. Potential antimicrobial agents should be tested for cytotoxicity and activity against non-related pathogens.

To help editors and referees assess the significance of each submitted manuscript we ask all authors on submission to provide a brief statement of significance. This should contain one sentence to summarise the most important finding(s) in the manuscript and a second sentence to say why this is a significant advance in the field. This significance statement should focus specifically on the importance of the piece of research being submitted, rather than the importance of the field.

RSC Medicinal Chemistry Lectureship award

This Lectureship celebrates outstanding early career researchers who have made significant contributions in the fields of medicinal chemistry and drug discovery. The RSC Medicinal Chemistry Lectureship is awarded annually through a process whereby nominations of candidates are invited from our community.

You can read about eligibility, how to nominate, deadlines for nominations and see all of our lectureship winners.

Find out who is on the editorial and advisory boards for the  RSC Medicinal Chemistry  journal.

Editor-in-chief

Mike Waring , Newcastle University, UK

Associate editors

Cynthia Dowd , George Washington University, USA

Maria Duca , Université Côte d’Azur - CNRS, France

Sankar K. Guchhait , National Institute of Pharmaceutical Education and Research (NIPER), India

Sally-Ann Poulsen , Griffith University, Queensland, Australia

Jian Zhang , Shanghai Jiao Tong University School of Medicine, China

Editorial board members

Hayley Binch , Hoffman-La Roche, Switzerland

Paola Castaldi , MatchPoint Therapeutics, USA

Lyn Jones , Dana-Farber Cancer Institute, USA

Jean-Louis Reymond , University of Bern, Switzerland

Timor Baasov , Israel Institute of Technology, Israel

Andreas Bender , University of Cambridge, UK

Julian Blagg , Institute of Cancer Research, UK

Margaret Brimble , University of Auckland, New Zealand

Mark Bunnage , Vertex, USA

Christopher Burns , Certa Therapeutics, Australia

Andrea Cavalli , University of Bologna, Italy

Young-Tae Chang , POSTECH, South Korea

James Crawford , Altos Labs, USA

Matthew Duncton , Rigel Pharmaceuticals Inc

Stephen Frye , University of North Carolina at Chapel Hill, USA

Matthew Fuchter , Imperial College London, UK

Sylvie Garneau-Tsodikova , University of Kentucky, USA

Jayanta Haldar , Jawaharlal Nehru Centre for Advanced Scientific Research, India

Gyoonhee Han , Yonsei University, Korea

Mike Hann , GSK Medicines Research Centre, Stevenage, UK

Christian Heinis , EPFL, Switzerland

Laura H. Heitman , Leiden University, Netherlands

Yoshinori Ikeura , Axcelead Drug Discovery Partners, Japan

Ahmed Kamal , NIPER, Hyderabad, India

Robert Langer , MIT, USA

Steven V Ley , University of Cambridge, UK

María Luz López Rodríguez , Complutense University of Madrid, Spain

Christa Muller , University of Bonn, Germany

Roberto Pellicciari , University of Perugia, Italy

David Rees , Astex Therapeutics, Cambridge, UK

Motonari Uesugi , Kyoto University, Japan

John C Vederas , University of Alberta, Canada

Paul Wender , Stanford University, USA

Zhen Yang , Peking University, China

Ming-Qiang Zhang , Amgen, Shanghai, China

Katie Lim , Executive Editor

Harriet Riley , Deputy Editor

Emily Cuffin-Munday , Development Editor

Sarah Anthony , Editorial Production Manager

Nicola Burton , Publishing Editor

Tom Cozens , Publishing Editor

Ryan Kean , Publishing Editor

Roxane Owen , Publishing Editor, ORCID  0000-0002-4553-233X

Lauren Yarrow-Wright , Publishing Editor

Andrea Whiteside , Publishing Assistant

Sam Keltie , Publisher, Journals, ORCID  0000-0002-9369-8414

Article types

RSC Medicinal Chemistry  publishes:

• Research articles
• Review articles

Research article

All new research in  RSC Medicinal Chemistry  is published in the Research article format. Research articles have no page limits, although most articles fall between 4 and 10 journal pages (approximately 10–25 pages of double-spaced text). Research Articles encompass both full paper and communication styles. Where a communication style article is submitted the work should be of enough importance to merit urgent publication before the full study is complete. In all cases authors should provide the same level of experimental detail and data (full details of requirements can be found in the “Journal Specific Guidelines” section below).

Research findings should be presented in an informative way, emphasising the importance and potential impact of the research. Authors should limit experimental procedures and data in the main text to a maximum two journal pages (approximately 5 double-spaced pages), with all additional experimental information and data placed in the electronic supplementary information (ESI).

Authors are particularly encouraged to prepare a title and abstract which concisely summarise the key findings of their research and their importance, avoiding the use of non-standard abbreviations, acronyms and symbols, as this will enable potential readers to quickly understand the significance of the research. Authors should also consider using recognisable, searchable terms, as around 70% of our readers come directly via search engines. The table of contents graphic should give the reader a clear indication of the topic of the study, for example by showing key compounds.

Authors are encouraged to use the article template, available from our  Author templates & services page , for preparing their submissions. However, the use of the template for Research article submissions is not essential.

Additional guidance on the layout and formatting of the article and supplementary information can be found on our  Prepare your article page .

Review article

These are easy-to-read articles covering current areas of interest for a broad medicinal chemistry audience. They are a concise and critical appraisal of an area in medicinal chemistry or a related topic, typically 6-12 pages in length. We also welcome shorter, mini-review style articles under this article type.

Reviews should focus on the key developments that have shaped the topic, rather than comprehensive reviews of the literature. Authors are encouraged to summarise important findings instead of re-iterating details already available in the primary work and should provide summary figures instead of multiple figures from original manuscripts, where appropriate.

Authors should include their own perspective on developments and trends, and the final paragraphs should discuss future directions, particularly identifying areas where further developments are imminent or that are in urgent need of being addressed.

Please note that Reviews should include balanced coverage of the field and not focus predominantly on the author’s own research.

Opinions are short, personal viewpoints on a topic of current interest to the community. They can be speculative in nature and stimulate counter-opinion, provided that they are not defamatory to the work of others. They should contain rigorous, evidence-backed scientific justification, and bring significant and valuable insights to the field.

Opinions are typically three to four pages in length and are normally published by invitation of the  RSC Medicinal Chemistry  Editorial Board or Editorial Office. Opinions undergo a rigorous and full peer review procedure, in the same way as Research and Review articles.

Comments and Replies are a medium for the discussion and exchange of scientific opinions between authors and readers concerning material published in  RSC Medicinal Chemistry .

For publication, a Comment should present an alternative analysis of and/or new insight into the previously published material. Any Reply should further the discussion presented in the original article and the Comment. Comments and Replies that contain any form of personal attack are not suitable for publication. 

Comments that are acceptable for publication will be forwarded to the authors of the work being discussed, and these authors will be given the opportunity to submit a Reply. The Comment and Reply will both be subject to rigorous peer review in consultation with the journal’s Editorial Board where appropriate. The Comment and Reply will be published together.

Transparent peer review

As part of our commitment to transparency and open science,  RSC Medicinal Chemistry  is now offering authors the option of transparent peer review, where the editor’s decision letter, reviewers’ comments and authors’ response for all versions of the manuscript will be published alongside the article under an  Open Access Creative Commons licence (CC-BY) .

Reviewers will remain anonymous unless they choose to sign their report.

Find out more about our transparent peer review policy

Journal specific guidelines

Human and animal welfare.

When a study involves the use of live animals or human subjects, authors must include in the 'methods/experimental' section of the manuscript a statement that all experiments were performed in compliance with the relevant laws and institutional guidelines, and must state the institutional committee(s) that has approved the experiments. A statement that informed consent was obtained for any experimentation with human subjects is required. Reviewers may be asked to comment specifically on any cases in which concerns arise.

More information on the Royal Society of Chemistry journals’ ethical policies can be found in our Author responsibilities page .

Disclosure of chemical structures

Chemical structures should be reported in the manuscript if that structure is necessary to understand the paper or repeat an experimental or computational procedure. Chemical structures should not be blanked out. In certain cases the non-disclosure of chemical structures may be acceptable, and these are considered on a case-by-case basis by the Associate Editor.

Experimental methods and data

Sufficient details of experimental or computational procedures should be included such that a scientist skilled in the art would be able to reproduce the results presented. The synthesis of all new compounds must be described in detail. Descriptions of synthetic procedures must include the specific reagents and solvents employed and must give the amounts (g, mmol) used. Products yields (%) must be reported together with a clear statement of how the percentage yields were calculated. The final physical state (solid; amorphous; liquid; solution) of the product should be disclosed. Where compounds are synthesised as part of an array or library a representative synthesis will be sufficient.

Authors should limit experimental procedures and data to two journal pages (approximately 5 double-spaced pages), with all additional experimental information and data placed in the electronic supplementary information (ESI).

Characterisation of organic compounds

Characterisation levels should be consistent with the importance of the compound to the conclusion of the work:

• For all tested compounds purity should be at least 95%, confirmed by either 1 H/ 13 C NMR data (with spectrum presented in the supplementary file), HPLC, GC, electrophoresis or elemental analysis. Further characterisation data should be supplied where available
• For key compounds (those which are subject to further study beyond initial screening), additional data should include 1 H NMR data (with spectrum presented in the supplementary file) and LC-MS data. Further data such as 13 C NMR, IR, CHN data and HRMS data should be supplied if available
• For chiral compounds, when used as a non-racemate, specific rotation and evidence of enantiomeric purity via chiral HPLC or derivatisation to diastereoisomeric compounds/use of chiral shift reagents should be given. Where HPLC is used conditions employed should be supplied including column type, flow rate, solvent system and detection method
• For compounds made as part of an array that are not considered key compounds, LC-MS data is sufficient.
• For compounds generated through combinatorial methods, lead compounds should be characterised to the same standards as compounds generated through standard synthetic procedures.
• For known compounds, an original reference to previously reported data should be cited; however authors should also include any new, previously unpublished characterisation data that have been obtained for known compounds.

Characterisation of biomolecules (For example, enzymes, peptides, proteins, DNA/RNA, oligosaccharides, oligonucleotides)

Authors should provide evidence for the identity and purity of the biomolecules described. The techniques that may be employed to substantiate identity include the following:

• Mass spectrometry
• Sequencing data (for proteins and oligonucleotides)
• High field 1 H, 13 C NMR
• X-ray crystallography

Purity must be established by one or more of the following:

• Gel electrophoresis
• Capillary electrophoresis
• High field 1 H, 13 C NMR.

Sequence verification should also be provided for nucleic acid cases involving molecular biology. For organic synthesis involving DNA, RNA oligonucleotides, their derivatives or mimics, purity must be established using HPLC and mass spectrometry as a minimum. For new derivatives comprising modified monomers, the usual organic chemistry analytical requirements for the novel monomer must be provided. However, it is not necessary to provide this level of characterisation for the oligonucleotide into which the novel monomer is incorporated.

Novel macromolecular structures and newly reported nucleic acid or protein sequences and microarray data must be deposited with the appropriate database. Articles will not be published until the relevant accession number has been provided. These codes should be quoted in the experimental section of the manuscript. Microarray data should be MIAME compliant.

All Western blot and other electrophoresis data should be supported by the underlying raw images. The image of the full gel and blot, uncropped and unprocessed, should be provided in the supplementary information on submission. All samples and controls used for a comparative analysis should be run on the same gel or blot.

When illustrating the result, any cropping or rearrangement of lanes within an image should be stated in the figure legend and with lane boundaries clearly delineated. Alterations should be kept to a minimum required for clarity.

Each image should be appropriately labelled, with closest molecular mass markers and lanes labelled. All details must be visible, over or underexposed gels and blots are not acceptable. Authors should be able to provide raw data for all replicate experiments upon request.

Biological data

Biological test methods should be described in sufficient detail such that a scientist skilled in the art would be able to reproduce the results presented. Forms of administration as well as physical states and formulations should be noted. Doses and concentrations should be expressed as molar quantities (for example, mol kg -1 , µmol kg -1 , M, µM). For those compounds found to be inactive, the highest concentration ( in vitro ) or dose level ( in vivo ) tested should be indicated. For in vivo studies vehicle information should be supplied.

Quantitative biological data are required for all test compounds. It is expected that all tested compounds would be 95% pure and shown to be so using standard methods. Active compounds from combinatorial syntheses should be re-synthesised and retested to verify biological activity. In these cases experimental procedures and characterisation data as described above should be provided. Known or standard compounds or drugs should be tested under the same experimental conditions for the purpose of comparison (as a positive control). Data may be presented in tabulated form or as graphs; extensive data for compounds should be presented in the electronic supplementary information. Authors should use a number of significant figures that is relevant to the accuracy of the data. Information about the error associated with biological data, for example standard deviation or SEM, should be provided along with the number of experimental determinations.

Pan Assay Interference (PAINS) Compounds

In cases where potential assay interference compounds (for example covalent modifiers, luminescent molecules, redox active compounds, metal chelators, membrane disruptors or unstable compounds which can decompose to form active compounds)are reported as being active, authors should provide evidence in the experimental section that this activity is genuine and is not due to an artefact. For more information about interference compounds see JB Baell and GA Holloway, J. Med. Chem. 2010, 53 , 2719-2740.

Computational studies

Details of the types of computational studies that are suitable for publication in RSC Medicinal Chemistry are given in the “Scope” section above.

Computational methods should be described in sufficient detail such that a scientist skilled in the art would be able to reproduce the results presented. Where computational studies are accompanied by experimental results (for example to validate a prediction) those experimental procedures and data should also be described in detail (see guidelines for experimental procedures above). Where an existing computational method is used authors should provide reasoning why this is appropriate for their study.

QSAR & QSPR studies

Studies which report new methodology or theory should be validated against at least one other common data set for which a study using another method has been published previously. Standard studies must be accompanied by new experimental data which tests their predictive power. To be considered for RSC Medicinal Chemistry  such studies should demonstrate significant potential to advance the field of medicinal chemistry. Any data or structures which are used to carry out a QSAR or QSPR study should either be made available as supplementary material, or be freely available elsewhere with a reference to the location included in the manuscript.

Statistical analysis

In articles where there is large-scale statistical analysis one of the named authors should be a statistician.

Guidelines on writing titles, abstracts & table of contents entry

The title, abstract and table of contents entry (graphical abstract) are the first parts of your manuscript that editors, referees and potential readers will see, and once published they play a major part in a researcher’s decision to read your article. Therefore it’s important that these clearly and concisely show the main findings of your research and why they are important.

The title should be short and straightforward to appeal to a general reader, but detailed enough to properly reflect the contents of the article.

• Keep it relatively short – between 8 and 15 words is ideal
• Use easily recognisable words and phrases that can be read quickly 
• Use general terms for compounds and procedures rather than specific nomenclature or very specialised terms
• Avoid using non-standard abbreviations and symbols
• Avoid using subjective terms such as “novel”
• Use keywords and familiar, searchable terms – these can increase the chances of your article appearing in search results. Around 70% of our readers come directly via search engines.

The abstract is a single paragraph which summarises the findings of your research. It will help readers to decide whether your article is of interest to them.

• The length can vary from 40 to 150 words, but it should always be concise and easy to read, with recognisable words and phrases.
• It should set out the objectives of the work, the key findings and why this research is important (compared to other research in its field).
• It should emphasise (but not overstate) the significance and potential impact of the research in your article.
• Avoid including detailed information on how the research was carried out. This should be described in the main part of the manuscript.
• Like your title, make sure you use familiar, searchable terms and keywords.

Table of contents entry

A table of contents entry (graphical abstract) is required, which should be submitted at the revision stage. This should include an eye-catching graphic and 1-2 sentence(s) of text to summarise the key findings of the article to the reader. It will appear in the table of contents and feeds – for example, RSS feeds.

The graphic should:

• Be simple, but informative.
• Capture the reader’s attention (the use of colour is encouraged).
• Include a structure, scheme, graph, drawing, photograph or combination that conveys the message of the article. Please note, complex schematics or spectra should be avoided.
• Be original, unpublished artwork created by one of the co-authors. Preferably, the graphic should not be reused and appear again within the article.
• Be suitable for, and uphold the standards of, a scholarly publication that has a global reach.
• Not contain any elements that are offensive or inappropriate, in particular words or images that are discriminatory.
• Not contain large amounts of text. Text should be limited to the labelling of compounds, reaction arrows and diagrams, with long phrases or sentences being avoided. Any text should be clearly legible to a reader.
• Not contain logos, trademarks or brands names.

The text should:

• Be concise and focus only on the key findings of the manuscript and their importance, not the processes used; think about what would grab the attention of the potential reader and would encourage them to read the full article.
• Avoid repeating or paraphrasing the title or abstract.
• Use easily recognisable words and phrases that can be read quickly.

Table of contents specifications:

• The figure should be a maximum size of 8 cm wide x 4 cm high.
• Figures should be supplied as TIFF files, with a resolution of 600 dpi or greater.
• The text supplied should be 1-2 sentences long, using a maximum of 250 characters.

Injectable peptide hydrogels for controlled-release of opioids From DOI:  10.1039/C5MD00440C

Drug trapping in hERG K +  channels: (not) a matter of drug size? From DOI:  10.1039/C5MD00443H

Structural hybridization of three aminoglycoside antibiotics yields a potent broad-spectrum bactericide that eludes bacterial resistance enzymes From DOI:  10.1039/C5MD00429B

Rigid amphipathic nucleosides suppress reproduction of the tick-borne encephalitis virus From DOI:  10.1039/C5MD00538H

Vast numbers of prevalent aminoglycoside-modifying enzymes undermine the clinical use of aminoglycoside antibiotics. We present the design and synthesis of a potent broad-spectrum bactericidal aminoglycoside based on available X-ray co-crystal structures within the ribosomal binding-site. The resulting antibiotic displays broad protection of its functional groups from inactivation by clinically relevant resistance enzymes.

From DOI:  10.1039/C5MD00429B

Advanced glycation end products (AGEs) are associated with various diseases, especially during aging and the development of diabetes and uremia. To better understand these biological processes, investigation of the in vivo kinetics of AGEs, i.e., analysis of trafficking and clearance properties, was carried out by molecular imaging. Following the preparation of Cy7.5-labeled AGE-albumin and intravenous injection in BALB/cA-nu/nu mice, noninvasive fluorescence kinetics analysis was performed. In vivo imaging and fluorescence microscopy analysis revealed that non-enzymatic AGEs were smoothly captured by scavenger cells in the liver, i.e., Kupffer and other sinusoidal cells, but were unable to be properly cleared from the body. Overall, these results highlight an important link between AGEs and various disorders

From DOI:  10.1039/C6OB00098C

A screen of 20 compounds identified small molecule adjuvants capable of potentiating antibiotic activity against  Francisella philomiragia . Analogue synthesis of an initial hit compound led to the discovery of a potentially new class of small molecule adjuvants containing an indole core. The lead compound was able to lower the MIC of colistin by 32-fold against intrinsically resistant  F. philomiragia .

From DOI:  10.1039/C5MD00353A

Table of contents

Structural modifications through bioisosteric approach yielded fusidic acid analogues with 2–35 folds increase in antiplasmodial activity as compared to fusidic acid. From DOI: 10.1039/C5MD00343A

The combination of flow chemistry and computational tools has been successfully applied to prepare a focused library of tricyclic tetrahydroquinolines endowed with drug-like properties. From DOI:  10.1039/C5MD00455A

A screen of 20 compounds identified small molecule adjuvants capable of potentiating antibiotic activity against  Francisella philomiragia . From DOI:  10.1039/C5MD00353A

A platinum complex/peptide chimera shows specific DNA binding and covalent platination with potential as a novel chemotherapeutic. From DOI:  10.1039/C5OB01885D

Open access publishing options

RSC Medicinal Chemistry  is a hybrid (transformative) journal and gives authors the choice of publishing their research either via the traditional subscription-based model or instead by choosing our gold open access option.  Find out more about our Transformative Journals. which are Plan S compliant .

Gold open access

For authors who want to publish their article gold open access , RSC Medicinal Chemistry  charges an article processing charge (APC) of £2,750 (+ any applicable tax). Our APC is all-inclusive and makes your article freely available online immediately, permanently, and includes your choice of Creative Commons licence (CC BY or CC BY-NC) at no extra cost. It is not a submission charge, so you only pay if your article is accepted for publication.

Learn more about publishing open access .

Read & Publish

If your institution has a Read & Publish agreement in place with the Royal Society of Chemistry, APCs for gold open access publishing in RSC Medicinal Chemistry  may already be covered.

Use our journal finder to check if your institution has an open access agreement with us.

Please use your official institutional email address to submit your manuscript and check you are assigned as the corresponding author; this helps us to identify if you are eligible for Read & Publish or other APC discounts.

Traditional subscription model

Authors can also publish in RSC Medicinal Chemistry via the traditional subscription model without needing to pay an APC. Articles published via this route are available to institutions and individuals who subscribe to the journal. Our standard licence allows you to make the accepted manuscript of your article freely available after a 12-month embargo period. This is known as the green route to open access.

Learn more about green open access .

Readership information

Researchers in academia and industry studying medicinal chemistry, pharmacology, and topics in the wider chemical, biological and materials sciences with application to biological problems.

Subscription information

RSC Medicinal Chemistry  is part of the RSC Gold subscription package.

Online only 2024 : ISSN 2632-8682, £1,709 / $2,533

*2023 Journal Citation Reports (Clarivate Analytics, 2024)

**The median time from submission to first decision including manuscripts rejected without peer review from the previous calendar year

***The median time from submission to first decision for peer-reviewed manuscripts from the previous calendar year

****CiteScore™ 2023 available at   www.scopus.com/sources

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RSC Medicinal Chemistry

An analysis of the physicochemical properties of oral drugs from 2000 to 2022.

Calculable physicochemical descriptors are a useful guide to assist compound design in medicinal chemistry. It is well established that controlling size, lipophilicity, hydrogen bonding, flexibility and shape, guided by descriptors that approximate to these properties, can greatly increase the chances of successful drug discovery. Many therapeutic targets and new modalities are incompatible with the optimal ranges of these properties and thus there is much interest in approaches to find oral drug candidates outside of this space. These considerations have been a focus for a while and hence we analysed the physicochemical properties of oral drugs approved by the FDA from 2000 to 2022 to assess if such concepts had influenced the output of the drug-discovery community. Our findings show that it is possible to find drug molecules that lie outside of the optimal descriptor ranges and that large molecules in particular (molecular weight >500 Da), can be oral drugs. The analysis suggests this is more likely if lipophilicity, hydrogen bonding and flexibility are controlled. Crude physicochemical descriptors are useful in that regard but more accurate and robust means of understanding substructural classes, shape and conformation are likely to be required to improve the chances of success in this space.

Supplementary files

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• Review Article
• Published: October 2004

A guide to drug discovery

The role of the medicinal chemist in drug discovery — then and now

• Joseph G. Lombardino 1 &
• John A. Lowe III 2  

Nature Reviews Drug Discovery volume  3 ,  pages 853–862 ( 2004 ) Cite this article

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Medicinal chemists paly a crucial role in the drug discovery process through the selection and synthesis of compounds that establish structure–activity relationships and achieve efficacy and safety in preclinical animal testing

Many aspects of the medicinal chemist's role have changed since the early era of drug discovery when animal testing and small, informal project teams dominated the process.

Combinatorial chemistry, high-throughput screening and molecularly defined targets that allow structure-based drug design have changed the chemist's role in the modern era.

In vitro screens for pharmacokinetic properties, the focus on synthesizing drug-like compounds, and in vitro toxicity screens are important new developments that aid the medicinal chemist's job today.

Suggestions for improving the drug discovery process include more in vivo testing earlier in the drug discovery process, allowing medicinal chemists to champion their drug candidate during its development; and passing on the tacit knowledge of experienced medicinal chemists to their younger colleagues.

The role of the medicinal chemist in drug discovery has undergone major changes in the past 25 years, mainly because of the introduction of technologies such as combinatorial chemistry and structure-based drug design. As medicinal chemists with more than 50 years of combined experience spanning the past four decades, we discuss this changing role using examples from our own and others' experience. This historical perspective could provide insights in to how to improve the current model for drug discovery by helping the medicinal chemist regain the creative role that contributed to past successes.

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Medicinal chemists prepare and/or select appropriate compounds for biological evaluation that, if found to be active, could serve as LEAD COMPOUNDS . They then evaluate the STRUCTURE–ACTIVITY RELATIONSHIPS (SARs) of analogous compounds with regard to their in vitro and in vivo efficacy and safety. Today, medicinal chemists who are engaged in drug discovery are part of interdisciplinary teams, and must therefore understand not only the field of organic chemistry, but also a range of other disciplines to anticipate problems and interpret developments to help move the project forward.

As highlighted in this article, the role of the medicinal chemist has changed significantly in the past 25 years. In the early era ('then') of drug discovery (1950 to about 1980), medicinal chemists relied primarily on data from in vivo testing. In the more recent ('now') period (about 1980 to the present), the development of new technologies, such as high-throughput in vitro screening, large compound libraries, COMBINATORIAL TECHNOLOGY , defined molecular targets and structure-based drug design, has changed that earlier and relatively simple landscape. Although these new technologies present many opportunities to the medicinal chemist, the multitude of new safety requirements that have arisen has also brought unanticipated hurdles for the task of translating in vitro activity to in vivo activity. Simultaneously, the knowledge base that supports drug research has expanded considerably, increasing the challenge for chemists to understand their fields of expertise. The demonstration of adequate clinical safety and efficacy in humans has also become more complex, and ever-increasing amounts of data are now required by regulatory agencies. In fact, despite the use of many new technologies, and the growing resources and funding for drug research, the number of launches of new medicines in the form of NEW MOLECULAR ENTITIES (NMEs) has been generally decreasing for more than a decade. Clearly, the difficulty and complexity of drug research has increased in the past two decades. It is our aim with this article to discuss how these changes have influenced the role of medicinal chemists and to suggest ways to help them to contribute more effectively to the drug discovery process.

The process of drug discovery

Inventing and developing a new medicine is a long, complex, costly and highly risky process that has few peers in the commercial world. Research and development (R&D) for most of the medicines available today has required 12–24 years for a single new medicine, from starting a project to the launch of a drug product ( Fig. 1 ). In addition, many expensive, long-term research projects completely fail to produce a marketable medicine. The cost for this overall process has escalated sharply to up to an estimated US $1.4 billion for a single new drug 1 . All of the funds to support this research usually come from the income of the private pharmaceutical company that sponsors the work. In the research ('R'; discovery) phase, only a fraction of the scientific hypotheses that form the basis for a project actually yield a drug candidate for development. In the drug development ('D') phase, experience has shown that only approximately 1 out of 15–25 drug candidates survives the detailed safety and efficacy testing (in animals and humans) required for it to become a marketed product. And for the few drug candidates that successfully become marketed products, some will not recover their costs of development in the competitive marketplace, and only approximately one in three will become a major commercial product. Clearly, this is a high-stakes, long-term and risky activity, but the potential benefits to the millions of patients with serious diseases provide a constant motivating force. At virtually every phase — from project initiation to discovery, development and planning for marketing for a new drug — the modern medicinal chemist can have a role.

The drug discovery process begins with the identification of a medical need, including a judgement on the adequacy of existing therapies (if there are any). From this analysis, together with an appraisal of the current knowledge about the target disease, will come hypotheses on how to possibly improve therapy — that is, what efficacy, safety or mechanistically novel improvements will advance the method of drug treatment for patients with the target disease? On the basis of these hypotheses, specific objectives will be set for the project. Then, testing selected chemicals in appropriate biological tests can begin. Key subsequent steps in the process include detecting relevant biological activity (a 'hit') for a structurally novel compound in vitro , then finding a related compound with in vivo activity in an appropriate animal model, followed by maximizing this activity through the preparation of analogous structures, and finally selecting one compound as the drug development candidate. This drug candidate then undergoes toxicological testing in animals, as required by law. If the compound passes all these tests, all the accumulated research data are assembled and submitted as an Investigational New Drug Application (IND) to the Food and Drug Administration (FDA) in the United States (or comparable agency in other countries) before clinical trials are initiated. In the clinic, there is sequential evaluation in normal human volunteers of toleration (Phase I), efficacy and dose range in patients (Phase II), followed by widespread trials in thousands of appropriate patients to develop a broad database of efficacy and safety. For the few (4–7%) drug candidates that survive this series of development trials, a New Drug Application (NDA) that contains all the accumulated research data is filed for thorough review by the experts at the FDA. Only with their approval can the new drug be offered to doctors and their patients to treat the disease for which it was designed.

The role of the medicinal chemist

The modern medicinal chemist, although part of a team, has a particularly crucial role in the early phases of drug discovery. The chemist, trained to prepare new chemicals and with an acquired knowledge of the target disease and of competitive drug therapies, has an important part in framing the hypothesis for the new drug project, which then sets the objectives for the project. The chemist also helps to decide which existing chemicals to screen for a lead compound and which screening hits need to be re-synthesized for biological evaluation. Purification and proper characterization of the new chemicals is also the responsibility of the chemist. When an in vitro ' HIT ' is identified, the chemist decides on what analogous compounds should be obtained or synthesized to explore the SARs for the structural family of compounds in an effort to maximize the desired activity. Developing in vivo activity for the hit compound in an appropriate animal model is also mainly the responsibility of the chemist. This can often be one of the most difficult steps to accomplish because several factors, such as absorbability, distribution in vivo , rate of metabolism and rate of excretion (ADME), all present hurdles for the chemist to solve in the design and preparation of new, analogous chemicals for testing. The goal at this stage is to maximize efficacy while minimizing side effects in an animal model.

For the medicinal chemist to address all the challenges outlined above, several skills are required. These include a thorough knowledge of modern organic chemistry and medicinal chemistry, an understanding of the biology that relates to the target disease, an understanding of the pharmacological tests used in the project and sufficient knowledge of the factors that influence ADME characteristics of chemicals in vivo . Furthermore, they should also have an understanding of clinical medicine that pertains to the target disease; knowledge of the regulatory requirements for related drugs; a current knowledge of competitive therapies, both in the market and under development by competitors; a thorough knowledge of the literature that is relevant to the target disease; familiarity with the many newer technologies available to facilitate drug discovery; and an entrepreneurial attitude in behaving as an innovator and inventor. Finally — and of crucial importance to the timely success of the project — the chemist must show superior interpersonal skills throughout the life of the project to interact effectively with colleagues from other disciplines to achieve project goals.

The medicinal chemist — then and now

Then (1950s–1980s). About 25–45 years ago, a medicinal chemist's tasks differed in some ways from those of a chemist today; an example of a successful project from this era (the development of the anti-inflammatory agent piroxicam (Feldene; Pfizer)) is highlighted in Box 1 . At that time, the medicinal chemist and a pharmacologist counterpart were the main drivers of the research programme: compounds were designed and individually synthesized by the chemist in gram quantities to accommodate the need for testing in whole animals by the pharmacologist. Given the limited synthetic methodology available, these syntheses were often time-consuming and, even with one or two technical assistants working in the laboratory, the output from one chemistry laboratory was limited to an average of one to three compounds per week. Commercially available starting materials were often limited. The chemist had only a few tools (for example, infrared and ultraviolet spectroscopy, and column chromatography) to assist with compound characterization and purification. Outsourcing was rare; all tasks, including bulk syntheses, toxicological testing and analogue synthesis, were done in-house. The creativity and intuition of the medicinal chemist was pivotal to the success of the programme, although given the limited number of compounds produced, serendipity had a large role as well.

Projects generally used in vivo models for primary screening, as little was known about the detailed biological mechanisms involved in most diseases. In vitro testing against a key enzyme or specific receptor involved in the disease process was usually not possible; as discussed in Box 2 (which describes the discovery of the antipsychotic ziprasidone (Geodon; Pfizer)), in vitro receptor-based pharmacology only became common in the 1980s and 1990s. In addition, compound collections for exploratory biological screening were limited. The data generated from the test models were compiled, analysed and displayed by hand in the form of charts and graphs. Similarly, searching the literature for relevant information involved the handling of bound volumes taken individually from the library shelves.

Small companies tend to rely on informal communication and timelines, and this was often the case in the smaller pharmaceutical industry 'then'. For the medicinal chemist, the benefit of this informality was ready access to colleagues in other disciplines to evaluate a compound that the chemist was interested in. The disadvantage came once a chemist's compound was selected for further development. The chemist, who would probably have moved on to another project, usually heard little or nothing about the drug candidate until the (often) bad news came back that the candidate had failed some key test. Keeping abreast of the progress of the drug candidate required the same proactive, informal action that the chemist had used previously to periodically contact the appropriate scientists in other disciplines to get some news about the drug candidate. To address these issues, most organizations in the 1980s established interdisciplinary matrix teams for each drug candidate to facilitate information exchange and joint planning between departments, such as chemistry, biology, pharmaceutics, toxicology, PHARMACOKINETICS , clinical medicine and regulatory affairs, all of which have important roles in drug development.

Overall, the process of drug discovery 'then' was slower and operated from a relatively smaller knowledge base. Several factors combined to slow the process: there was less known about diseases, there were fewer available compounds to screen, there were no computerized technologies for handling information and data, there was a need to manually search the literature, there was a need to individually prepare gram quantities of each new compound for testing, and chemists rarely received information from other disciplines about their development candidates. On the other hand, once a lead was identified in the primary in vivo test model, many of the pharmacokinetic (ADME) problems were mainly in hand or could be rapidly addressed, thereby expediting the selection of a drug candidate to study in the clinic.

Now (1980s–present). Despite some differences from the earlier era of drug discovery described above, medicinal chemists today face many of the same tasks and challenges that they did 40 years ago. So, the chemist still selects the appropriate structural series of compounds to follow and pursues the SARs to identify suitable drug candidates for advancement to safety and clinical testing. But today's chemist has a much wider range of tools to help overcome the numerous hurdles in the drug discovery process. These new tools include advances in synthetic, analytical and purification technology, such as transition-metal-catalysed carbon–carbon bond-forming reactions, high-field NMR and preparative high-performance liquid chromatography (HPLC), as well as computer-assisted literature and data retrieval and analysis. The recent trend towards outsourcing many routine, tedious aspects of the drug discovery process has freed today's chemist to spend more time on new compound design. In addition, two powerful technologies have put numbers on the chemist's side: combinatorial chemistry (combichem) and high-throughput screening (HTS). Combichem allows chemists to generate rational, focused libraries of compounds that define SARs in a fraction of the time that was required 'then'. Depending on where they work, chemists can design, synthesize and purify libraries themselves, or hand over the final synthesis steps to a group of chemists designated for this purpose. This group might also make lead-compound libraries that target specific receptor or enzyme families to provide better quality leads that are suitable for library follow up. The development of HTS of large sample collections, including the designed libraries, has produced marked decreases in the personnel, time and money required to identify compounds that hit a specific biological target, although many companies are struggling to triage the large number of screening hits to viable lead compounds that can support a successful drug discovery project. In this struggle, costs can escalate significantly as the generation of large amounts of data is not the same as generating viable, quality leads. Finally, new graphics software, such as Excel and Spotfire 2 , can facilitate the retrieval and analysis of the mountain of data generated from screening compound libraries in a large panel of in vitro assays.

The molecular genetics revolution 3 has driven the development of another key ingredient in today's drug discovery model: the use of molecularly defined biological targets, such as enzymes, receptors and transporters. The desire for defined molecular targets for drug discovery, in contrast to the clinically based animal-model approach used in the early era of drug discovery discussed above, derives from several factors. One is the advantage of a known mechanism of action over a 'black-box' (that is, unknown) mechanism obtained from animal-model testing that could produce unanticipated toxicity during drug development. Another is the use of structure-based drug design, which allows the chemist to design new compounds by directly visualizing the interaction of a lead compound with the target protein through X-ray crystallographic analysis, but which is only possible with a molecularly defined target protein 4 . A recent example from the new era of drug discovery described in Box 3 (the kinase inhibitor imatinib mesylate (Gleevec; Novartis)) illustrates these advantages, which are now so well established that retreat to the black-box models of yesteryear is no longer feasible.

Recent changes — medicinal chemistry today

New techniques for addressing pharmacokinetic issues. The emphasis on in vitro screening of compounds against molecularly defined targets, although rapid and specific, has additional consequences for today's medicinal chemist. As the primary screen used to guide SAR studies, in vitro data do not help chemists to overcome the pharmacokinetic liabilities of their compounds. On the other hand, relying on in vivo animal models for the evaluation of pharmacokinetic performance suffers from a potentially serious drawback: differences between absorption and metabolism of drugs in humans and rats (a common test species) can lead to the development of drugs that work only in rats and not in humans. To help overcome this limitation, in vitro screens have been developed that are predictive of human pharmacokinetic performance, for example, by measuring a compound's degradation by preparations of human microsomes or hepatocytes or by recombinant human CYTOCHROME P450 ENZYMES . In addition to assessing metabolic stability, P450 assays can determine whether a compound is likely to interfere with the metabolism of other drugs that a patient is taking by virtue of inhibiting the P450 enzyme required for their elimination. Permeability and transporter assays have also been developed to characterize drug uptake into or efflux from the target organ(s) (for a review of the P-glycoprotein (Pgp) transporter in drug development, see Ref. 5 ). So, today's chemist has a complex array of in vitro SAR patterns to discern and interpret to plan the preparation of compounds for follow up (for a review of the screening data typically used in the drug discovery process, see Ref. 6 ). Selected compounds must also be profiled in vivo to assess how well the in vitro data predict in vivo performance. Further in vivo testing is then required to show that the compound attains levels at the target organ commensurate with achieving the desired biological effect that is proposed to result from the in vitro activity.

Final testing might involve a disease-relevant animal model, although these data must be interpreted cautiously owing to several limitations. For example, many diseases, such as stroke , atherosclerosis and Alzheimer's disease , do not have clinically effective drugs that can validate a disease-progression-relevant animal model. Also, older models are based on drugs that work by certain mechanisms, and might not fairly assess drugs that are developed against a new mechanism. As such, the disease-relevant animal model is only one of many assays used to evaluate new compounds and, coming later in the testing sequence, has less impact on decisions made by today's chemists.

Synthesis of 'drug-like' compounds. Another strategy to overcome pharmacokinetic liabilities is the prediction and synthesis of compounds with ' DRUG-LIKE ' properties. Highly lipophilic, high-molecular-mass compounds tend to have more potent in vitro binding activity, by virtue of excluding water from the enzyme or receptor surface and thereby picking up additional hydrophobic interactions. But these compounds are usually not drug-like because of their low water solubility, and they generally fail in further development because of poor pharmacokinetics and oral BIOAVAILABILITY . Lipinski et al . 7 formulated the 'rule-of-five' to predict drug-likeness, which consists of four important properties, each related to the number 5 (molecular mass <500 Da; calculated LOGP <5; hydrogen-bond donors <5; and hydrogen-bond acceptors <10). The rule is based on data in the literature for a large number of compounds, including all known drugs, that correlate physical properties with oral bioavailability. Support for the rule as a predictor of drug-likeness comes from observing weaknesses in the development pipelines of major pharmaceutical companies owing to failure to adhere to the rule-of-five 8 . Computational calculations routinely predict rule-of-five properties for prospective compounds in a chemist's SAR plans to guide compound selection, although this guidance comes at the cost of adding complexity to an already complex set of in vitro data.

Use of in vitro toxicity screens to reduce attrition. Completing the in vitro screens that the chemist uses to select the next compound to synthesize are the toxicity screens that weed out compounds predicted to fail for safety reasons. The Ames test, and related in vitro tests for mutagenicity and carcinogenicity, has a long history, but recent additions to this list include the hERG channel, a cardiac potassium ion channel involved in cardiac repolarization following ventricle contraction during the heartbeat 9 . Drugs that bind to and inhibit the hERG channel can cause prolongation of the QT interval of the electrocardiogram, leading to loss of a synchronous heartbeat and eventually ventricular fibrillation, and even death. The danger posed by a drug that inhibits the hERG channel was illustrated by the deaths of patients taking the allergic rhinitis drug astemizole (Hismanal; Janssen), which led to its abrupt withdrawal from the market 10 . In the aftermath of this and other incidents of fatal complications from hERG-blocking drugs, the FDA is formulating guidelines to address the issue. Most pharmaceutical companies now have hERG screening in place to afford chemists an indication of the therapeutic index of their compounds for this end point 11 .

Box 4 summarizes the various criteria that today's chemist must follow to develop a successful drug candidate. A recent literature example that illustrates many of the new techniques and testing hurdles for today's medicinal chemist — a series of farnesyl transferase inhibitors — is given in Box 5 .

Final thoughts on the drug discovery process

The role of a champion in drug discovery. As a scientist involved at the very earliest stages of drug discovery, including the setting of project objectives, the medicinal chemist with leadership qualities has the opportunity to act as a champion for the drug candidate throughout the long R&D process. Championing a drug candidate was often a key factor in a successful drug project 'then' and was facilitated by the smaller project teams typical of this earlier era. For example, key publications concerning a new drug often had just two authors, the chemist and the biologist, who were essentially the drug champions. There is a multitude of commercially successful drugs today that survived a dark period during development only because a champion worked to keep the drug alive by finding answers to problems (see examples provided in Ref. 12 ).

To act as a champion for a drug candidate, a chemist with current knowledge of all aspects of the drug programme must take an enduring, pervasive interest in all aspects of the development process, especially in helping to solve those seemingly intractable challenges that inevitably arise during the long path to regulatory approval. Without a champion, a drug candidate can lose momentum and stall irreversibly during the years leading to regulatory approval. This is truer today than ever, because the process has become so much more complicated. And yet the contribution of a medicinal chemist can seem diluted by the presence of scientists from the many other disciplines that make up a typical drug discovery programme today, disciplines which have risen significantly in importance in recent years. In addition to the increased number of contributing scientific sub-specialities today, the high cost and increased complexity of drug R&D today 1 can dwarf any one scientist's contribution.

Suggestions for improving the drug discovery process. Recent data indicate that productivity has not kept pace with increasing resource allocation to the drug discovery process. We would like to suggest three ways to improve the current model for new drug discovery that would help the medicinal chemist to be more productive. The first stems from the current heavy reliance on in vitro screening for driving SARs early in a programme, at the risk of finding poor pharmacokinetics and oral bioavailability later on. Coordinating animal testing with in vitro testing early in the drug discovery process to pre-screen lead series in vivo , and then correlating in vitro pharmacokinetics screens with in vivo data as soon as possible, might provide a firmer footing for the chemist to overcome any deficiencies in pharmacokinetics. Such testing might also help to identify lead compounds on the basis of their promising in vivo activity or pharmacokinetic properties that would have been rejected on the basis of in vitro testing alone.

The second suggestion is based on the need to have a committed drug champion to bring background information and a historical perspective (sometimes termed 'institutional memory'), and to suggest solutions to the myriad issues that arise throughout a drug's development. By appointing a small, permanent committee, which includes the medicinal chemist from the discovery team, to be involved with the entire drug development programme through to drug registration (and to work alongside the interdisciplinary matrix development teams), there would always be someone available to provide informed judgments on the basis of their medicinal chemistry background and experience on the project to help keep the drug on track during the many years required for its successful development.

Finally, as many of the most experienced chemists in the pharmaceutical industry reach retirement age, there remains the challenge of how to pass on their learning to the next generation. They possess tacit knowledge (that is, residing in the mind of the experienced scientist but not yet communicated to others) of the drug discovery experience that needs to be recognized, captured and then passed on to the young scientists (as outlined in Ref. 13 ). Companies that accomplish this, by, for example, holding in-house workshops on drug design and lecture series on medicinal chemistry, will help to teach the next generation of scientists the art of successful drug discovery.

The changing landscape of the pharmaceutical industry. Some basic questions about the new technologies and procedures now used for drug research, compared with the dwindling supply of new drugs approved in recent years, have been raised in recent news articles 14 , 15 , 16 , 17 . For example, has the introduction of major changes in the drug discovery process caused the obvious drop in new drug output? Is this drop temporary, to last only until the new technologies begin to yield some products? Have the changes produced a decrease in output by stifling the creativity of the scientists (including the medicinal chemists) involved in drug discovery? Has the role of serendipity, so important to drug discovery in the past, been supplanted by robots? What has happened to the role of the medicinal chemist's intuition and creativity in producing quality drugs? How many of today's most successful drugs could have been made through the limited chemical pathways offered by combichem techniques? Making millions of new chemicals robotically does not, apparently, lead to more new drugs.

An important perspective on this discussion comes from a recent account 17 of the key differences in the pharmaceutical industry experienced by a father–son pair of medicinal chemists, Leo Sternbach ('then', about 40–50 years ago, when he invented chlordiazepoxide (Librium; Hoffman-La Roche) and diazepam (Valium; Hoffman-La Roche)) and his son, Daniel ('now', currently a medicinal chemist at GlaxoSmithKline). By their account, the role of the medicinal chemist has changed considerably from that of a highly autonomous, independent inventor 'then' to a significant player in a large team that is increasingly influenced by the business units 'now'.

In our opinion, whatever the merits of the business decisions that led to this change, the role of serendipity, chemical intuition and creativity in thoughtfully selecting a chemical target to synthesize in order to discover the best-quality drugs has not diminished. There must always be an opportunity in research for the useful chance observation by a prepared mind. There are many examples of 'back burner' (that is, unauthorized) projects that have yielded important new drugs. Although the new technologies that have accelerated the process of drug discovery provide some undoubted benefits, the human factor remains an integral part of success in this endeavour. It is our hope that the accounts of successful drug discoveries presented here will serve as a reminder of the chemists whose decisions actually led to these success stories.

Today, the rapidly expanding knowledge base concerning diseases, their causes, symptoms and their effects on the human body holds great promise for the discovery of important new medicines. Sequencing the human genome also offers the opportunity for finding many more novel and selective therapies. Such discoveries will probably come from teams of scientists, including medicinal chemists, whose careers are devoted to this one task. The enormous cost of this task will be borne mainly by those pharmaceutical companies that can successfully generate the required research funds from the sale of their existing drugs.

Medicinal chemists today live in exciting times. They are key participants in the effort to produce more selective, more effective and safer medicines to treat the diseases of mankind. Their work can have a beneficial effect on millions of suffering patients — surely an important motivating factor for any scientist.

Box 1 | Discovery of piroxicam (1962–1980)

The project that produced the novel anti-arthritic and anti-inflammatory agent piroxicam (Feldene; Pfizer) began in 1962 and led to the product launching into key European markets in 1980. A detailed history of this 18-year process, including the failures and setbacks along the way, has been described elsewhere 12 , 18 , so only a brief outline will be given here.

The original research team assigned to produce a new anti-inflammatory agent at Pfizer consisted of just two people — a medicinal chemist and a pharmacologist. Both were new to the area of inflammation research and had to educate themselves on all aspects of this therapeutic area. Several therapies for treating the symptoms of arthritis were already available or in development at other companies. These therapies included aspirin, indomethacin, diclofenac, ibuprofen and others. The medicinal chemist noted that all of these agents were from one chemical class — the carboxylic acids. Members of this chemical class were known to be rapidly metabolized and excreted, therefore necessitating multiple daily dosing (three to six times a day) of these drugs to maintain control of the pain and swelling of arthritis. These multiple daily doses were a feature that patients found to be undesirable and led to poor compliance. Furthermore, high daily doses (up to 16 g of aspirin) were required for some of these relatively non-potent agents, therefore placing a heavy load on the gastrointestinal tract, liver and kidneys, and consequently increasing the potential for toxicity.

In the early period of the project that eventually produced piroxicam, a set of project objectives were gradually developed that guided the project in the succeeding years. These objectives were to:

seek a structurally novel compound with acidic properties, but not a carboxylic acid.

seek a highly potent anti-inflammatory agent in animal models that was predictive of clinical activity and to use as controls the drugs known to be efficacious in humans.

identify an active agent that resists metabolism that would produce a long plasma half-life in animals and in humans, and consequently lead to reduced frequency of dosing in humans.

seek a very safe agent that arthritic patients could use over long periods of time to treat their chronic disease.

These stringent objectives placed formidable hurdles in the pathway to success and prolonged the time required to successfully achieve the goal.

The synthesis of gram quantities of compounds designed by the chemist then began, all of which were thought to have the potential to fulfill the project objectives. The acidity (p K a ) of each structure was measured and the serum half-life in dogs was determined for selected analogues to guide the synthesis programme. Using in vivo animal models of inflammation (this was before prostaglandins were known to be involved in inflammation), several families of compounds were found and partially developed ( a–d ), but each failed during a 5-year period (reviewed in Ref. 12 ) before the first 'oxicam' shown in panel e (CP-14304) was synthesized (see figure). The synthesis of this particular compound was a 'back burner' probe based on the intuition of the chemist. The introduction of a carboxamide function into the molecule proved to be a key factor in increasing anti-inflammatory activity and for increasing acidity. Structure–activity relationships (SARs) for several hundred analogous oxicam structures produced improved activity and safety, and, eventually, through a series of three development candidates (see figure parts c and e ), led to piroxicam as the agent that best met the project objectives. Extensive clinical trials confirmed the efficacy and safety of the new drug, leading to approvals and launches into major European markets in 1980, 18 years after the project was started. The drug provided around-the-clock symptom control for arthritis patients with just one 20-mg dose per day, leading to widespread acceptance by patients and making Feldene one of the most successful drugs in the 1980s. After 1992, major protective patents expired and generic brands of piroxicam dominated the market.

Box 2 | Discovery of ziprasidone (1984–2001)

Ziprasidone (Geodon; Pfizer) was launched in 2001 for the treatment of schizophrenia, a debilitating mental disease characterized by delusions, social withdrawal, suicidal behaviour and cognitive decline. The project that led to the discovery of ziprasidone relied primarily on disease-relevant animal models as had piroxicam ( Box 1 ), but, in addition, in vitro receptor-binding assays helped to find an agent that would lead to a significant advance over the already-available treatment.

The disease-relevant animal models for the ziprasidone discovery programme go back to the 1950s and the discovery of the first drug for schizophrenia (chlorpromazine), an anti-allergy drug that was serendipitously found to produce a calming effect in psychotic patients 19 . Paul Janssen, who had set up a medical research laboratory in 1953, studied the potential for discovering new antipsychotic drugs based on chlorpromazine by using it as a control drug in animal models designed to predict clinical activity. The models that Janssen developed relied on the ability of chlorpromazine to block the locomotor effects of stimulants such as amphetamine and apomorphine. Testing new agents that mimicked this activity of chlorpromazine led to his discovery of the first-generation antipsychotic drug haloperidol 20 . These models were still being used in the 1980s and therefore contributed to the discovery of ziprasidone.

As a supplementary approach to in vivo animal models as the primary screen, in vitro receptor-based pharmacology emerged in the 1980s and 1990s and came to dominate the field of antipsychotic drug research. This was based on the finding that agents such as haloperidol are effective antipsychotic drugs at the mechanistic level by virtue of their blockade of dopamine type 2 (D 2 ) receptors. In addition, clozapine — the first 'atypical' antipsychotic drug (so-called because it lacks the undesirable motor side effects of haloperidol and chlorpromazine, known as extrapyramidal symptoms (EPS)) — binds to both D 2 and 5-hydroxytryptamine type 2 (5-HT 2 ) receptors. The 5-HT 2 receptor for the neurotransmitter serotonin is thought to afford protection from EPSs that are caused by excessive D 2 -receptor blockade 21 , and this hypothesis initiated a search for an agent with a favourable (>10-fold) ratio of D 2 - to 5-HT 2 -receptor blockade 22 .

The search for ziprasidone began by considering the structure of naphthylpiperazine (compound 1 in the figure). Compound 1 was reported to be a potent ligand for serotonin receptors, including the 5-HT 2 receptor 23 . Combining compound 1 with the structure of dopamine, the natural ligand for the D 2 receptor, and then substituting the catechol with an oxindole as a surrogate produced the combined D 2 and 5-HT 2 antagonist compound 2 (see figure). Compound 2 seemed to be the perfect antipsychotic agent, at least in rats 24 . Further testing in monkeys, however, was disappointing, and attention switched to a new series derived from the 1,2-benzisothiazole group, which proved to have even more potent D 2 -receptor blockade while adding potent 5-HT 2 -receptor blockade that afforded the desired D 2 /5-HT 2 ratio 25 . Fine-tuning of the structure–activity relationship in this new series led from the prototype compound 3 to compound 4 (ziprasidone; see figure) 26 . Finally, the discovery programme confirmed the validity of the D 2 /5-HT 2 hypothesis using disease-relevant animal-model testing, which demonstrated efficacy without EPS liability. Following the 5-year-long discovery phase, another 9 years of clinical testing and 3 years to address regulatory requirements were needed before approval of ziprasidone was given by the FDA. Extensive clinical testing validated the discovery approach, and today hundreds of thousands of patient-days of use have demonstrated the efficacy and safety of ziprasidone as it continues to help patients afflicted with this lifelong, devastating disease.

Box 3 | Discovery of imatinib mesylate

An illustration of the role of a defined molecular target coupled with structure-based drug design in drug discovery comes from the story of imatinib mesylate (Gleevec; Novartis), a selective tyrosine kinase inhibitor approved for the treatment of CHRONIC MYELOGENOUS LEUKAEMIA . The discovery of the oncogenes in the 1970s promised to aid the discovery of oncological drugs with reduced toxicity. In contrast to the cancer drugs in use then, which nonspecifically inhibited DNA synthesis and cell division, an oncogene inhibitor should be selectively toxic to cancer cells. Zimmerman and the Novartis group chose the tyrosine kinase BCR–ABL — which is created by a reciprocal chromosomal translocation that produces the BCR–ABL gene — as their target, as it is found only in leukaemic cells 27 . Inhibiting this molecularly defined target therefore reduces toxicity and maximizes the desired therapeutic effect. They chose compound 1 (see figure), an inhibitor of protein kinase C, as the starting point for the medicinal chemistry programme. Addition of the amide and methyl groups to the phenyl ring (see figure, compound 2) added the potency and selectivity needed for BCR–ABL inhibition, and addition of the piperazinylmethyl group (to generate imatinib, compound 3) was required for water solubility and oral bioavailability. Here is where the second advantage of a defined molecular target provides a crucial insight: when the X-ray crystal structure of imatinib bound to BCR–ABL was solved, it was found that the piperazine ring made significant contacts with the enzyme and was not just providing improved water solubility 28 . More importantly, these X-ray structure data provide insight into how mutations in the BCR–ABL gene produce an imatinib-resistant form of the enzyme, which offers the potential for designing new drugs to overcome this resistance.

Box 4 | In vitro tests: 'now' and 'then'

The following is a typical battery of tests for a modern drug discovery programme 'today'; those marked with an asterisk were also in use 'then'.

In vitro target

Selectivity assays

In vitro absorption, distribution, metabolism and elimination (ADME)

Microsomal stability

Hepatocyte stability

P450 substrate

P450 inhibitor

Permeability

Transporter efflux (for example, P-glycoprotein)

Protein binding

Physical properties

Rule-of-five

In silico ADME

* Secondary (behavioural, chronic)

* Ames test

Micronucleus test

hERG half-maximal inhibitory concentration (IC 50 )

P450 induction

Broad screening

* Others (depending on project)

Box 5 | Farnesyl transferase inhibitors

As one of the oncogenes characterized in the 1970s, RAS has been the target of numerous drug discovery efforts. Compounds that inhibit the enzyme farnesyl transferase (FTase) prevent the mutant form of RAS from causing tumour formation. A group at Merck has published extensively 29 on their FTase inhibitor programme, and examples from this programme are shown in the figure.

The table in the figure shows data for a set of compounds illustrating the criteria that the Merck group used to evaluate their compounds 30 . Compound 1 shows potent in vitro activity for the primary endpoint, farnesyl transferase (FTase) inhibition (IC 50 values are shown), as well as selectivity against geranyl geranyl transferase type I (GGTase), required for cell viability (IC 50 values are shown). Even though it shows good oral bioavailability (F) — 81% — it inhibits the hERG channel (the inflection point for binding to the hERG channel by radioligand displacement assay (hERG IP) = 440 nM) and causes QT PROLONGATION in the dog at a dose that is unacceptable. Macrocyclization to give compound 2 overcomes the problem with inhibition of hERG while maintaining in vitro potency, selectivity and oral bioavailability. In addition, X-ray crystal structure data of compound 2 bound to FTase explain how the enzyme accommodates this structural change and aids in further drug design. Increasing flexibility by saturating one of the rings of the naphthyl core in compound 2 to produce compound 3 and compound 4 considerably increases in vitro potency. Compound 3, however, is unfortunately very potent at hERG (80 nM), whereas compound 4 is cleared rapidly (rate of plasma clearance in the dog (CLp) = 7.3 ml per min per kg). So, even though it is the least potent compound in the set, compound 2 is the best choice for further structure–activity relationship development, primarily because of its pharmacokinetics and safety margin. This example illustrates why today's chemist more often prefers to begin with compounds that possess better pharmacokinetic and selectivity properties, and then to proceed to optimize potency for the primary in vitro end point. (Func 1, cell-based radiotracer assay for FTase inhibition; Func 2, cell-based assay for inhibition of FTase substrate derivatization, given in the absence and presence of human serum; N/A, not available; P450, IC 50 value for inhibition of human P450 3A4.)

R&D execs paint bleak picture of industry productivity: $1.4 bil. per NME. The Pink Sheet 6 (18 August 2003).

Demesmaeker, M. in Proc. 13th European Symp. Quantitative Structure-Activity Relationships: Rational Approaches to Drug Design (eds Hoeltje, H.-D. & Sippl, W.) 506–511 (Prous Science, Barcelona, 2000).

Google Scholar  

Chanda, S. K. & Caldwell, J. S. Fulfilling the promise: drug discovery in the post-genomic era. Drug Discov. Today 8 , 168–174 (2003).

Article   CAS   Google Scholar  

Reich, S. H. & Webber, S. E. Structure-based drug design (SBDD): every structure tells a story. Perspect. Drug Discov. Design 1 , 371–390 (1993).

Lin, J. H. & Yamazaki, M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. 42 , 59–98 (2003).

Lin, J. et al. The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Curr. Top. Med. Chem. 3 , 1125–1154 (2003). An excellent summary of the screening paradigm used in big pharma to evaluate new compounds for suitability as development candidates.

Article   Google Scholar  

Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 46 , 3–26 (2001). A classic paper that outlines the use of physical properties to predict 'drug-likeness', used by most pharmaceutical companies to guide drug design.

Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44 , 235–249 (2000).

Tseng, G. -N. IKr: The hERG channel. J. Mol. Cell. Cardiol. 33 , 835–849 (2001).

Taglialatela, M. et al. Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity. Clin. Exp. Allergy 29 (Suppl. 3), 182–189 (1999).

Redfern, W. S. et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc. Res. 58 , 32–45 (2003).

Wiseman, E. H. & Lombardino, J. G. in Chronicles of Drug Discovery Ch. 8 (eds Bindra, J. S. & Lednicer, D.) 173–200 (J. Wiley and Sons, Inc., New York, 1982). An account of the discovery of the novel anti-inflammatory drug piroxicam.

Sapienza, A. M. & Lombardino, J. G. Recognizing, appreciating, and capturing tacit knowledge of R & D scientists. Drug Dev. Res. 57 , 51–57 (2002).

Mullen, R. Priming the pipeline. Chem. Eng. News 82 , 23–42 (2004).

Landers, P. Drug industry's big push into technology falls short. The Wall Street Journal A1 (24 February 2004).

Big Trouble for Big Pharma. The Economist 14 (16 December 2003).

Flynn, J. In two generations, drug research sees a big shift. The Wall Street Journal A1 (11 February 2004). An account of the careers of Leo Sternbach, inventor of Valium, and his son, Daniel, contrasting their experiences in drug discovery.

Lombardino, J. G. & Wiseman, E. H. Nonsteroidal Antiinflammatory Drugs — Mechanisms and Clinical Use Ch. 26 (eds Lewis, A. & Furst, D.) 487–506 (Marcel Dekker Inc., New York, 1987).

Delay, J., Deniker, P., Green, A. & Mordret, M. Excitor-motor syndromes provoked by ataratics. Presse Medicale (1893–1971), 65 , 1771–1774 (1957).

CAS   PubMed   Google Scholar  

Granger, B. The discovery of haloperidol. Encephale , 25 , 59–66 (1999).

Hippius, H. A historical perspective of clozapine. J. Clin. Psychiatry 60 (Suppl. 12), 22–23 (1999). An account of the development history of the first atypical antipsychotic drug clozapine.

PubMed   Google Scholar  

Pere, J. J. Clinical psychopharmacology: the example of clozapine (Leponex). Encephale 21 (Spec. No. 3), 9–12 (1999).

Glennon, R. A., Slusher, R. M., Lyon, R. A., Titeler, M. & McKenney, J. D. 5-HT1 and 5-HT2: binding characteristics of some quipazine analogs. J. Med. Chem. 29 , 2375–2380 (1986).

Lowe, J. A. et al. 1-naphthylpiperazine derivatives as potential atypical antipsychotic agents. J. Med. Chem. 34 , 1860–1866 (1991).

Lowe, J. A. Atypical antipsychotics based on the D2/5-HT2 ratio hypothesis. Curr. Med. Chem. 1 , 50–60 (1994).

CAS   Google Scholar  

Howard, H. R. et al.. 3-benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J. Med. Chem. 39 , 143–148 (1996). An account of the discovery of the atypical antipsychotic drug ziprasidone.

Capdeville, R., Buchdunger, E., Zimmermann, J. & Matter, A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nature Rev. Drug Discov. 1 , 493–502 (2002). An account of the design and discovery of the anticancer drug imatinib mesylate (Gleevec; Novartis).

Schindler, T. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289 , 1938–1942 (2000).

Bell, I. M. et al. 3-aminopyrrolidinones farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. J. Med. Chem. 45 , 2388–2409 (2002). An account of a recent programme to discover novel anticancer agents that inhibit farnesyl transferase. Some of these data come from reference 30.

Bell, I. M. et al. Design and biological activity of ( S )-4-(5-{[1-(3-Chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl}imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency. J. Med. Chem. 44 , 2933–2949 (2001).

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A chemical structure or series of structures that show activity and selectivity in a pharmacological or biochemically relevant screen.

The correlation of structural features with the activity of compounds in a given assay.

Synthetic technologies to generate compound libraries rather than single compounds.

(NME). A medication containing an active ingredient that has not been previously approved for marketing in the United States in any form.

A biologically active compound that exceeds a certain activity threshold in a given assay.

The study of the absorption, distribution, metabolism, excretion and interactions of a drug.

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Sharing certain characteristics with other molecules that act as drugs. The set of characteristics — such as size, shape and solubility in water and organic solvents — varies depending on who is evaluating the molecules.

The fraction or percentage of an administered drug or other substance that becomes available in plasma or to the target tissue after administration.

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Human ether-a-go-go-related gene, the gene that encodes the α-subunit of the I Kr channel, a major determinant of human cardiac repolarization.

The QT interval is a measure of the total time of ventricular depolarization and repolarization. In recent years, several drugs have been withdrawn from the market because of unexpected reports of sudden cardiac death associated with prolongation of the QT interval. Blockade of the hERG channel has been linked to this effect.

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Lombardino, J., Lowe, J. The role of the medicinal chemist in drug discovery — then and now. Nat Rev Drug Discov 3 , 853–862 (2004). https://doi.org/10.1038/nrd1523

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Application of data-driven blended online-offline teaching in medicinal chemistry for pharmacy students: a randomized comparison

Yong-ming zhao.

1 Department of Pharmacy, Hebei North University, Zhangjiakou, China

2 Hebei Key Laboratory of Neuropharmacology, Zhangjiakou, China

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The data used and analyzed during the current study are available from the corresponding author on reasonable request.

The purpose of this study was to evaluate the effectiveness and efficiency of implementing a data-driven blended online-offline (DDBOO) teaching approach in the medicinal chemistry course.

A total of 118 third-year students majoring in pharmacy were enrolled from September 2021 to January 2022. The participants were randomly assigned to either the DDBOO teaching group or the traditional lecture-based learning (LBL) group for medicinal chemistry. Pre- and post-class quizzes were administered, along with an anonymous questionnaire distributed to both groups to assess students’ perceptions and experiences.

There was no significant difference in the pre-class quiz scores between the DDBOO and LBL groups ( T =-0.637, P  = 0.822). However, after class, the mean quiz score of the DDBOO group was significantly higher than that of the LBL group ( T  = 3.742, P  < 0.001). Furthermore, the scores for learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, innovation ability, and satisfaction, as measured by the questionnaire, were significantly higher in the DDBOO group than in the traditional group (all P  < 0.05).

The DDBOO teaching method effectively enhances students’ academic performance and satisfaction. Further research and promotion of this approach are warranted.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12909-024-05701-x.

Introduction

With the comprehensive integration of information technology in the field of education, traditional classrooms have evolved with various new models of online teaching, making the instructional process more dynamic and effective [ 1 ]. Learners are encouraged to engage in online learning tasks and digital game-based activities, experiencing the joy of dealing with digital challenges, acquiring knowledge, and enhancing learning outcomes [ 2 , 3 ]. These emerging technologies serve as crucial tools for information dissemination in online education, profoundly impacting the reform of medical school education [ 4 ].

Blended learning, an instructional model combining digital online learning with face-to-face classroom teaching, has gradually drawn more attention with advancements in internet technology and education [ 5 , 6 ]. The concept of blended learning was first introduced in the U.S. National Education Technology Plan. Since 2004, the United States has been actively adopted and innovated the blended learning approach, continually exploring advancements in technology and other aspects.

Higher education has undergone a significant evolution in teaching paradigms. Following eras of experiential imitation teaching and computer-assisted instruction [ 7 ], the current landscape is increasingly characterized by the data-driven instruction [ 8 ]. This approach incorporates next-generation information technologies such as the Internet of Things, big data, cloud computing, and mobile internet, involving systematic collection and analysis of both online and offline learning data to inform instructional improvements and elevate learning outcomes [ 9 ].

Data-driven instruction is an innovative approach that harnesses diverse forms of data to shape and enhance teaching practices [ 10 ]. This encompasses a spectrum from summative data, such as test scores, to formative data gauging student understanding through activities like discussions. Diverging from summative assessments primarily designed for assigning grades, formative assessments aim to refine teaching methods. The collection and analysis of both types of data empower educators to discern patterns and address shortcomings within their classrooms. Through the strategic utilization of these insights, educators can tailor instruction to individual student needs, pinpoint specific areas for improvement, and implement timely interventions to bolster overall student success. This proactive and personalized approach to teaching ensures that educators are equipped with the necessary information to optimize learning experiences and foster positive educational outcomes for every student.

Medicinal chemistry is a comprehensive discipline focused on the discovery and invention of new drugs, the synthesis of chemical pharmaceuticals, elucidating the chemical properties of drugs, and researching the interaction patterns between drug molecules and cellular entities. Its scope encompasses the chemical structure, physicochemical properties, preparation methods, transport metabolism, structure-activity relationships, chemical mechanisms of drug action, as well as approaches and methods for the discovery of new drugs [ 11 ]. With the continuous deepening of educational reforms, the teaching approach in medicinal chemistry has shifted from traditional methods towards a blended learning model [ 12 , 13 ]. This approach seamlessly integrates online and offline teaching, leveraging the advantages of interactive communication in face-to-face classrooms while overcoming the limitations of traditional offline teaching, such as a singular format and limited content. Moreover, the use of online resources in the blended learning model has expanded the platform for medicinal chemistry education, greatly enriching the teaching content. It has not only sparked students’ interest in learning but also broadened their perspectives. Therefore, it is essential to explore the application of the blended learning model in biochemistry teaching.

Teaching medicinal chemistry presents a unique challenge for pharmacy students, prompting a preliminary investigation into the data-driven blended online-offline teaching model’s implementation. This instructional approach amalgamates various teaching techniques with the objective of improving students’ learning outcomes and satisfaction, thereby offering additional teaching avenues for nurturing pharmaceutical talent.

Participants

This teaching reform experiment is open to all third-year Pharmacy students at Hebei North University. Before commencing the experiment, students were required to complete a short screening questionnaire to ensure they had the necessary resource for the experiments. The questionnaire asked the following five yes-or-no questions: (1) Do you have a stable internet connection? (2) Do you have access to an independent electronic device (laptop, tablet, or smartphone)? (3) Are you able to complete the online course? (4) Are you able to complete the exams and questionnaires? (5) Are you aware of this experiment and willing to participate? Students who answered “yes” to all questions were eligible for the study, while those who answered “no” to one or more questions were excluded.

Sample size, grouping and blinding methods

According to the sample size calculation method reported in the literature [ 14 ], the study required a minimum of 52 participants per group to achieve a significance level (α) of less than 0.05 and a power (1-β) of 80%. The participants were randomly divided into experimental group ( n  = 59) and control group ( n  = 59) using a simple randomization. Both groups were supervised by the same teaching team, including one professor and two assistants. The experiment was conducted using a single-blind method and the students were blinded after assignment to interventions.

Study design

We have employed a randomized controlled trail to assess the effectiveness of a data-driven blended online-offline (DDBOO) teaching model on a group of healthy volunteers. The DDBOO method was implemented in the experimental group, while the control group received the traditional lecture-based learning (LBL).

Interventions

The ddboo model for medicinal chemistry course.

The DDBOO instructional process is structured into three phases: pre-class, in-class, and post-class. Through a seamless integration of synchronous and asynchronous learning, we have formulated a comprehensive DDBOO teaching approach, as illustrated in Fig.  1 .

An overview of the study design

Before class

The teacher introduces the theme, characteristics and tasks of the lesson online, emphasizing the importance of the chapter and sparking student’s interest. Students engage in self-directed online learning tasks utilizing the SuperStarLearn software. They access and complete tasks at their own pace, view microlecture videos covering key topics, and subsequently undergo corresponding chapter tests. Following this, Problem-based learning (PBL) scenarios are introduced, encouraging collaborative teamwork to address PBL tasks. For those who do not complete assigned tasks, the learning alert system prompts them to do so. Teachers analyze online learning data, including the duration and frequency of student video views and chapter test accuracy, to identify common issues and pinpoint teaching challenges.

During the class, teachers provide comprehensive explanations for commonly challenging issues and assess the learning outcomes through features such as quick response and in-class quizzes on the SuperStarLearn platform. Group discussions and collaborative thinking are encouraged to achieve a deeper understanding. Teachers also provide individualized guidance to address specific issues encountered by students during the learning process. By analyzing learning behaviors, such as participation in quick response and thematic discussions, as well as statistical data from in-class quizzes and assessments of group tasks, teachers can determine student engagement, personalized challenges, and learning effectiveness. This analysis enables teachers to intervene promptly, making adjustments to the teaching pace as necessary.

At the end of the class, the students completed a post-quiz and a questionnaire consisting of nine questions. Following the class, learning data retrieved from the SuperStarLearn Platform reports are used to distribute personalized assignments. By analyzing data such as assignment accuracy, teachers identified cognitive gaps and deviations among students. This information allows for targeted supplementation and correction in the subsequent class.

LBL method for medicinal chemistry course

In the control group, the same topics were presented through LBL. The lectures comprised two sessions, conducted once a week for 90 min each. During the class, the routine included the teacher explaining the learning objectives (5 min), delivering the content using PowerPoint slides (65 min), engaging in exercises (10 min), and participating in a class discussion or question-and-answer session (10 min). Students had the opportunity to participate in a question-and-answer session during the lecture, and discussions were encouraged if students wished to share their opinions or respond to their peers’ questions.

Outcome measurements

After obtaining informed consent, basic information about the participants, including age and gender, was collected. To evaluate students’ comprehension and application of knowledge, both groups underwent the same assessments, consisting of one pre-quiz and one post-quiz, each lasting 60 min and scored out of 100 points. Additionally, a questionnaire survey was administered at the end of the course to measure students’ self-perceived competence. The details of the questionnaire are presented in the Supplementary materials. This survey covered various aspects such as learning interest, targeted learning, motivation, self-learning skills, mastery of basic knowledge, teamwork abilities, problem-solving proficiency, and innovation capacity. Responses were rated using a 5-level Likert scale: 5 points for “strongly agreed,” 4 points for “agreed,” 3 points for “neutral,” 2 points for “disagreed,” and 1 point for " strongly disagreed.” Furthermore, a survey on satisfaction with the teaching mode was conducted, with responses categorized into four levels: “Very Satisfied,” “Satisfied,” “Neutral,” and “Dissatisfied.” In order to maintain impartial responses, both quizzes and questionnaires were conducted anonymously, mitigating any potential influence, whether positive or negative, on the students.

Statistical analysis

A chi-squared test (symbolically represented as χ 2 ) was employed to assess the discrepancy of count data. To compare two independent groups, the student t-test was utilized. Data were expressed as individual values and as mean ± standard deviation (SD). Statistical analysis was conducted using IBM SPSS statistics 20.0 software. The significance level (alpha) was set to 0.05, and p-values less than 0.05 were considered statistically significant.

Baseline characteristics of the students

From September 2020 to January 2021, a total of 118 students actively participated in the teaching experiment. Among them, 46 students were male (38.98%), and 72 students were female (61.02%). The average age of the participants was 20.5 ± 0.7 years. These students were randomly assigned to two groups: the DDBOO group ( n  = 59) and the traditional LBL group ( n  = 59). Notably, all students successfully completed the entire teaching process, including quizzes and questionnaires, and there were no dropouts during the study period. A comprehensive analysis of demographic data between the DDBOO group and the LBL group is presented in Table  1 . The results revealed no significant differences between the two groups in terms of gender ( P  = 0.45), age ( P  = 0.673), and pre-quiz scores related to basic knowledge ( P  = 0.822).

Comparison of basic data between two groups

Comparison of the post-quiz test scores between two groups

As illustrated in Fig.  2 , the statistical analysis of the box plots depicting final exam scores reveals that the average scores of the DDBOO group are higher than those of the LBL group( T  = 3.742, P  < 0.001). Moreover, there is a reduction in the number of low-scoring students, suggesting a better mastery of professional knowledge among students in the DDBOO group.

Comparison of the post-class test scores between two groups

Comparison of self-perceived competence and satisfaction between the two groups

A comprehensive evaluation of the teaching effectiveness between the DDBOO teaching method and the traditional LBL teaching approach was conducted through a post-teaching questionnaire survey. All questionnaires distributed for the survey were successfully collected and proved to be valid. According to Table  2 , the DDBOO group outperformed the LBL group in various aspects, including learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, and innovation ability, demonstrating statistically significant differences ( P  < 0.05). While the score for learning targeted was higher in the DDBOO group compared to the LBL group, this difference was not statistically significant ( P  > 0.05). Furthermore, as indicated in Table  3 , the level of satisfaction within the DDBOO group surpassed that of the traditional LBL group ( P  = 0.011).

Outcome of questionnaire (agree %)

Comparison of satisfaction with the course between two groups

Utilizing SPSS software for data analysis, we conducted a correlation analysis to further examine the relationship between students’ online and offline learning behaviors and their final exam scores under the DDBOO teaching model. The correlation analysis results are depicted in Fig.  3 . From Fig.  3 , it is evident that the online test scores demonstrates a positively correlation with final exam scores ( r  = 0.52), signifying a noteworthy impact of students’ performance in self-directed learning on overall learning quality. However, the correlations between visitation frequency, online video viewing duration, assignment scores and final scores are not significant. This may be attributed to some students engaging in online activities solely for the purpose of improving their scores. In addition to carefully designing online teaching activities, teachers need to appropriately assign weights to evaluation criteria for online self-directed learning, guiding students towards effective independent learning practices. Regarding offline learning behaviors, course interaction, PBL implementation, and classroom discussions exhibit higher correlations with final exam scores, with correlation coefficients of 0.53, 0.48 and 0.43, respectively. This suggests that classroom interactions and presentation discussions contribute to deepening students’ understanding and mastery of the learned content.

Correlation analysis of learning behaviors

The feedback results from the instructional survey indicate that the DDBOO teaching approach has achieved learning outcomes, as depicted in Fig.  4 . 91.5% of students believe that data-driven blended teaching has enhanced their study habit, transformed cognitive patterns, and bolstered subjective initiative. Additionally, 94.9% of students express that classroom interaction is more dynamic, encouraging them to confidently pose questions and articulate their viewpoints. The majority of students acknowledge the significant impact of data-driven blended teaching on overall skill enhancement, particularly in terms of autonomous learning, problem analysis, and teamwork abilities.

Results of the feedback of DDBOO group

This study investigated the effectiveness of a DDBOO teaching approach in medicinal chemistry for pharmacy students. The DDBOO model, integrating online resources with traditional classroom instruction, yielded significant improvements in students’ comprehension application of complex pharmaceutical concepts, and self-perceived competence as measured by post-course surveys. These findings not only highlight the effectiveness of DDBOO model, but also align with existing research on blended learning’s benefits, including flexibility, diverse resources, and enhanced student engagement [ 15 ]. Furthermore, DDBOO facilitates real-time feedback, adaptability, and a shift from teacher-centered learning to active problem-solving and collaboration. Data-driven assessments further empower instructors by allowing for early intervention and ongoing refinement of teaching methods based on student performance data [ 16 ]. This combined approach paves the way for optimizing student learning and engagement in medicinal chemistry education.

Blended online-offline teaching addresses pharmacy students’ need for practical skills by freeing up classroom time for hands-on practice [ 17 , 18 ]. Online platforms enable flexible, self-paced learning of theoretical knowledge outside of class, maximizing learning efficiency. This organic integration of theory and practice fosters the development of comprehensive abilities, including operational skills, critical thinking, and innovation. Students appreciate the flexibility and diverse resources offered by the blended approach, leading to increased engagement and enjoyment of the learning process.

The teacher plays a pivotal role in blended online-offline teaching for medicinal chemistry. They design a curriculum integrating both online and offline components, selecting materials tailored to medicinal chemistry education. Utilizing online platforms and resources, teachers engage students in various activities such as discussions and virtual experiments, guiding them through the online learning environment. Moreover, teachers adopt a data-driven approach, collecting and analyzing student performance data to provide individualized support and targeted interventions. Continuous feedback on student performance informs the adaptation of teaching strategies to meet diverse learning needs. Offline sessions, including laboratory work and group discussions, complement online components to offer a comprehensive learning experience. Through these efforts, teachers create a supportive and collaborative environment, fostering student interaction and critical thinking [ 19 ]. Overall, the teacher acts as a facilitator, guide, and analyst, utilizing data-driven insights to optimize the blended online-offline teaching approach in medicinal chemistry.

Limitations.

Despite its advantages, the DDBOO teaching model also presents several limitations. One notable limitation is the potential for unequal access to technology and online resources among students, which may widen existing educational inequalities. Additionally, the success of the DDBOO model relies heavily on effective technology integration and teacher training, which may pose challenges for institutions with limited resources or infrastructure. Moreover, the model’s effectiveness may vary depending on factors such as student motivation, prior knowledge, and learning preferences, highlighting the need for further research to better understand its impact across different contexts and populations. Overall, while the DDBOO teaching model offers numerous benefits for enhancing student learning and engagement, careful consideration of its limitations is essential for its successful implementation and long-term sustainability.

In conclusion, the application of the data-driven blended online-offline teaching model in medicinal chemistry for pharmacy students has demonstrated promising results in enhancing learning outcomes and satisfaction levels. This innovative approach, guided by big data technology, provides a tailored and personalized learning experience that addressed individual student needs. The findings of this study underscore the potential of integrating advanced teaching methodologies with traditional classroom instruction to optimize the educational experience in pharmacy education. Future research should explore the applicability of this blended teaching model to other disciplines, such as clinical medicine, nursing, and public health.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Acknowledgements

Not applicable.

Abbreviations

Author contributions

Si-si Liu and Jin Wang participated in the implementation of the project, and revision of the article. Yong-ming Zhao participated in the data collection and the writing of the article.

Hebei North University Project (No. XJ2024026). Hebei Provincial Higher Education Teaching Reform and Practice Project (No. 2021GJJG343).

Data availability

Declarations.

This study was assessed and approved by the Ethics Committee of Hebei North University. We confrm that all methods were conducted in accordance with relevant guidelines and regulations.

The authors declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Drugs and vaccines could be freed from cold chains by hydrogel

By Victoria Corless 2024-07-31T08:30:00+01:00

• No comments

A stiff hydrogel could end the need for vaccines and gene therapies to be refrigerated, potentially revolutionising the storage and transportation of vital, life-saving medicines.

Source: © Renata Angerami/Getty Images

Many medicines currently depend on cold chain technology to keep the drugs functional. However, refrigeration is expensive and not always available in remote areas leading to a search for other ways to keep vaccines and other medicines stable

Cold supply chain management is currently the best solution suppliers have for keeping active biological molecules, like mRNA, proteins and viruses, stable during distribution. However, it requires specialised handling and infrastructure, and incurs significant energy costs, limiting distribution.

‘A single ultralow temperature freezer can use as much electricity per day as a small household,’ says study author Matthew Gibson at the University of Manchester. ‘Addressing this may help with sustainability but crucially [would] allow advanced therapies to be shared more widely … to locations with less developed energy infrastructure.’

‘My team has been looking at cryopreservation for over a decade,’ he adds. ‘We have looked in the past at freezing proteins and had noticed that if we stopped the proteins aggregating, they survived the freezing quite well.’

This line of thinking led Gibson and his team to collaborate with Dave Adams at the University of Glasgow, whose group specialises in low molecular weight gelators – molecules that self-assemble into fibrous 3D networks, trapping large volumes of liquids in the process.

Gibson points out that proteins don’t just fall apart or unfold at room temperature. The issue is that they clump together and stop functioning. But to aggregate, proteins need to find and interact with one another – something easily done in a room temperature solution where they are free to move. ‘The network stops the proteins being able to move so freely and so [they can’t] aggregate,’ Adams explains.

Hydrogels have been used before in an effort to solve this problem. But where previous iterations have used chemical bonds to ‘tie’ proteins to the hydrogel’s polymers, the current approach yields stiff hydrogels that ‘freeze’ the proteins in place without the need to alter them.

‘Where you attach the polymer can change the structure and function of the biologic greatly,’ says Lydia Kisley of Case Western Reserve University, US, who was not involved in the study.

The gel’s rigidity, while great for stabilising biologics, also makes the hydrogel susceptible to breaking. However, the team do not see this as a weakness. ‘Many people try to get over this in various ways but we saw this as an advantage – if they break easily when you put strain on them, we reasoned it would be possible to use this to get the proteins back again without the need for any fancy chemistry,’ Adams says. ‘This gives us a cheap way of trapping the proteins, stopping the aggregation and getting the protein back.’

After some initial tests, the team settled on a gel that forms in the presence of a conventional buffer and its mechanical properties can be tuned by simply adding a calcium salt. The stiff hydrogel was found to stabilise proteins against thermal denaturation even at 50°C and, unlike other similar technologies, it delivers pure protein from a syringe.

Source: © Simona Bianco et al, Nature, 2024

The gels’ structure could be controlled with the addition of a calcium salt (right)

‘This is an interesting combination of materials science with biopharmaceuticals to overcome the tedious storage conditions for biologics,’ comments Kisley. ‘[They] take advantage of what many would consider a problem – the breakage of the gel under strain – as instead a positive to release the protein as it is pushed through a filtered syringe. This is a simple, yet overlooked, idea.’

However, these stiff hydrogels are not ready to begin dismantling drugs’ cold chains yet. ‘The model tests were limited to two relatively small proteins [but] many biologic therapies are large, antibody-based treatments,’ says Kisley. ‘Would the gelator still be able to self assemble and form the entangled network to trap large biologics? I wonder if the gelator would be able to maintain its properties with large molecules present.’

‘Any new technology has limitations,’ Gibson responds, ‘and we are exploring the range of proteins we can stabilise. Our discovery has an opportunity to be a platform technology but is adaptable to different use cases depending on the stressors involved.’

S Bianco et al , Nature , 2024, 631 , 544 (DOI: 10.1038/s41586-024-07580-0 ) 

• Drug formulation and delivery
• Medicinal chemistry
• Soft matter

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