RSC Medicinal Chemistry Blog

RSC Medicinal Chemistry is delighted to present our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Editorial Board member Professor Lyn Jones (Dana-Farber Cancer Institute, USA). Take a look at which articles he chose and why.

Lyn’s favourite articles

Discovery of an orally bioavailable, CNS active pan-mutant RET kinase heterobifunctional degrader

Douglas L. Orsi, Kiel E. Lazarski, Reina Improgo, R. V. Agafonov, Jae Young Ahn, Joelle Baddour, Katelyn Cassidy, Prasoon Chaturvedi, Kyle S. Cole, Richard W. Deibler, W. Austin Elam, Mark E. Fitzgerald, Victoria J. Garza, Andrew Good, Christopher H. Hulton, Marta Isasa, Katrina L. Jackson, Ping Li, Yanke Liang, Ryan E. Michael, Morgan Welzel O’Shea, Moses Moustakim, Samantha Perino, Fazlur Rahman, Matthew J. Schnaderbeck, Nicholas P. Stone, Bonnie Tillotson, Gesine K. Veits, Abigail Vogelaar, Jeremy L. Yap, Robert T. Yu, Hongwei Huang and James A. Henderson*

RSC Med. Chem., 2025, 16, 4781-4795

Lyn‘s comments:

“This study delivers a first-of-its-kind RET degrader – oral, brain-penetrant, and pan-mutant – designed to outsmart resistance where inhibitors fall short.”

Analysis of the structural diversity of heterocycles amongst European medicines agency approved pharmaceuticals (2014–2023) (Open Access)

Matthew Ward & Niamh M. O’Boyle*

RSC Med. Chem., 2025, 16, 4540-45770

Lyn’s comments:

“A simple yet important analysis of heterocycles found in drugs – essential reading for trainee medicinal chemists.”

A twist in the tale: shifting from covalent targeting of a tyrosine in JAK3 to a lysine in MK2 (Open Access)

Laura Hillebrand, Guiqun Wang, Alexander Rasch, Benedikt Masberg, Apirat Chaikuad, Thales Kronenberger, Ellen Günther, Michael Forster, Antti Poso, Michael Lämmerhofer, Stefan A. Laufer, Stefan Knapp and Matthias Gehringer*

RSC Med. Chem., 2025, 16, 4906-4919

Lyn’s comments:

“This paper explores tyrosine-targeted covalent inhibition in kinases, revealing unexpected lysine engagement by a fluorosulfate MK2 inhibitor and highlighting the untapped potential of nontraditional electrophiles.”

Meet the Editor

Lyn Jones, RSC Medicinal Chemistry Editorial Board member Lyn Jones completed his PhD studies in synthetic organic chemistry at the University of Nottingham, and his postdoctoral research at The Scripps Research Institute, California in chemical biology. He joined Pfizer Sandwich (UK) as a medicinal chemistry team leader, eventually becoming Head of Chemical Biology and Lead Discovery Technologies. He transferred to Pfizer Cambridge (USA) to become Head of Rare Disease Chemistry, and Head of Chemical Biology. He then helped establish Jnana Therapeutics as Head of Chemistry and Chemical Biology, before moving to Dana-Farber Cancer Institute in Boston as Chief Scientist of the Center for Protein Degradation. He is currently Principal Investigator and Faculty Member of the Department of Pediatric Oncology and Chemical Biology Program at DFCI, and his lab focusses on the development of next-generation covalent chemical biology with the objective of expanding the druggable proteome. He has been recognized with Royal Society of Chemistry awards for his contributions to HIV, COPD and rare genetic disease research. He has considerable experience working in many other disease areas, including cancer, inflammation, and pain. He is also an elected Fellow of the Royal Society of Chemistry, the Royal Society of Biology, and the Linnean Society, and was recently recognized as a Fellow of the American Association for the Advancement of Science, and as Fellow of the Learned Society of Wales, for his contributions to the field of medicinal chemistry and chemical biology.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

RSC Medicinal Chemistry is delighted to present our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Editorial Board member Dr Susanne Müller-Knapp (Goethe University Frankfurt, Germany). Take a look at which articles she chose and why.

Susanne’s favourite articles

Design and synthesis of a chemically diverse, lead-like DNA-encoded library from sequential amide coupling (Open Access) Cameron E. Taylor, Grace Roper, Rhianna Young, Fredrik Svensson, Andreas Brunschweiger, Sam Butterworth, Andrew G. Leach and Michael J. Waring* RSC Med. Chem., 2025, 16, 4774-4780

Susanne‘s comments:

“This article describes the details of the chemistry and enzymatic steps involved in the design and synthesis of a medium-sized DEL library using straightforward amide coupling methods.”

Expanding the reaction toolbox for nanoscale direct-to-biology PROTAC synthesis and biological evaluation Rebecca Stevens, Harry J. Shrives, Jenni Cryan, Diana Klimaszewska, Peter Stacey, Glenn A. Burley, John D. Harling, David J. Battersby* and Afjal H. Miah* RSC Med. Chem., 2025, 16, 1141-1150

Susanne‘s comments:

“Direct to biology approaches are an emerging area in the field of targeted protein degradation. In this research article, the approach has been combined with high-throughput chemistry based on key chemical reactions, namely reductive amination, SNAr, Pd-mediated cross-coupling and alkylation to accelerate generation of degrader molecules.”

Recent advances from computer-aided drug design to artificial intelligence drug design Keran Wang, Yanwen Huang, Yan Wang*, Qidong You* and Lei Wang* RSC Med. Chem., 2024, 15, 3978-4000

Susanne’s comments:

“In this review article, both computer-aided drug design as well as the emerging role of evolving role of artificial intelligence in drug discovery are discussed with a focus on chemical library screening, linker generation, and de novo molecular generation.”

Meet the Editor

Susanne Müller-Knapp, RSC Medicinal Chemistry Associate Editor Goethe University Frankfurt, Germany Susanne Müller-Knapp is Chief Operating Officer at the Structural Genomics Consortium, SGC, Frankfurt and Director of Operations of the Chemical Probes Portal. She obtained a PhD at the Karolinska Institute in Stockholm, Sweden. After spending several years as postdoctoral researcher in the area of inflammation and gene regulation at the Karolinska Institute and at the DIBIT San Raffaele Scientific Institute in Milan, Italy, she joined 2004 the SGC, at Oxford University, where she coordinated the Epigenetic Probe Project and lead a group, focusing on the evaluation of novel chemical probes, cellular target engagement of these tool compounds and their biological roles. Her research now focuses on using chemical biology to dissect the role of specific targets in biology and disease with a main focus on cancer. In her role as Director of Operations for the Chemical Probes Portal, she focuses on providing data and knowledge on high quality chemical tools and establishing quality standards for chemical probes with diverse modes of action.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

RSC Medicinal Chemistry is delighted to present our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Editorial Board member Dr Hayley Binch (Hoffman-La Roche, Switzerland). Take a look at which articles she chose and why.

Hayley’s favourite articles

The medicinal chemistry evolution of antibody–drug conjugates Adrian D. Hobson* RSC Med. Chem., 2024, 15, 809-831

Hayley’s comments:

“This article written from a medicinal chemistry perspective provides specific and detailed molecular optimization insights, especially for the linker and payload, which have a disproportionately massive impact on the ADC’s overall properties.”

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Target agnostic cellular screening in the era of chemically induced proximity Meizhong Jin* RSC Med. Chem., 2025, 16, 4532-4539

Hayley’s comments:

“This review highlights the significant potential of target agnostic cellular screening when leveraged with chemically induced proximity, a revolutionary new paradigm in drug discovery, to identify novel, difficult-to-predict opportunities for disease intervention. This is especially crucial given the growing challenges and increasing complexity encountered with target-focused methodologies.”

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Prodrugs and their activation mechanisms for brain drug delivery (Open Access) Ida Aaberg Lillethorup, Andreas Victor Hemmingsen and Katrine Qvortrup* RSC Med. Chem., 2025, 16, 1037-1048

Hayley’s comments:

“This review provides unique and detailed insights by systematically summarizing the specific activation mechanisms used to ensure prodrug selectivity within the Central Nervous System. This focus on the “back-end” activation process, rather than primarily on Blood-Brain Barrier transport distinguishes it from other reviews that concentrate mainly on carrier-mediated transport systems or general strategies for crossing the barrier.”

Meet the Editor

Hayley Binch, RSC Medicinal Chemistry Editorial Board Member Hoffman-La Roche, Switzerland Dr Hayley Binch is Head of Medicinal Chemistry at Hoffmann-La Roche in Basel. She obtained her PhD at the University of Bristol, UK in the field of Organic Chemistry, followed by postdoctoral research at the University of Hamburg, Germany and King’s College London. In 1998, she joined the Medicinal Chemistry department of Vertex Pharmaceuticals, Oxford, focussing on kinase research in the field of Oncology. In 2006, she moved to Vertex San Diego to work on ion channels for pain and cystic fibrosis. In 2016, she joined as a Section Head within Medicinal Chemistry at Hoffmann-La Roche in Basel and subsequently became Head of Medicinal Chemistry in 2017. At Roche, the Medicinal Chemistry department supports the design and synthesis of small molecules to identify clinical candidates in the areas of Immunology, Infectious Diseases, Neuroscience, Oncology, Ophthalmology and Rare Diseases.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

RSC Medicinal Chemistry is delighted to present our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Associate Editor Sally-Ann Poulsen (Griffith University, Australia). Take a look at which articles she chose and why.

Sally-Ann’s favourite articles

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Property-based optimisation of PROTACs James S. Scott*, Iacovos N. Michaelides and Markus Schade RSC Med. Chem., 2025, 16, 449-456

Sally-Ann’s comments:

“In this Opinion article the challenges faced by those working in the PROTAC field is discussed against the backdrop of the promise of this new frontier in drug development. I chose this manuscript as it prompts us to remain open minded about what is possible in the field of medicinal chemistry. As the journals’ readership has committed their careers to advancing medicinal chemistry, I hope the take aways in this Opinion article are relevant to their own research.”

Cytotoxicity of phosphoramidate, bis-amidate and cycloSal prodrug metabolites against tumour and normal cells (Open Access) Rebecca E. Farrell, Harrison Steele, Ryan J. Middleton, Danielle Skropeta* and Guo-Jun Liu* RSC Med. Chem., 2024, 15, 1973-1981

Sally-Ann’s comments:

“This manuscript describes some important aspects in the development of prodrugs including the assessment of potential off-target activity of prodrug metabolites vital in the drug design and biological evaluation process. This study spotlights the close link between classical medicinal chemistry and chemical probe development, where a range of experimental considerations are vital to generate valuable results.”

Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system (Open Access) Elisabeth Kallert, Laura Almena Rodriguez, Jan-Åke Husmann, Kathrin Blatt and Christian Kersten* RSC Med. Chem., 2024, 15, 1527-1538

Sally-Ann’s comments:

“This paper focuses on intentional targeting of RNA for drug discovery and contributes to the development of methods to identify small molecules for binding to RNA. As methods are still largely under development, of interest is the combination of structure-based virtual screening with biophysical screening methods.”

Meet the Editor

Sally-Ann Poulsen, RSC Medicinal Chemistry Associate Editor Griffith University, Australia Sally-Ann Poulsen is at the Institute for Biomedicine and Glycomics, Griffith University, Brisbane, Australia. She holds a PhD in medicinal chemistry also from Griffith University, receiving a University Medal for academic excellence. Immediately following her PhD, she was recipient of a Royal Society & National Health and Medical Research Council (NHMRC) Howard Florey Research Fellowship to undertake research at the University of Cambridge. On returning to Australia, she was awarded an Australian Research Council QEII Fellowship, followed by an Australian Research Council Future Fellowship. Sally-Ann works with collaborators in Australia and internationally, both from academia and industry on projects related to the development of new chemical probes for pathogens such as malaria and giardia and the application of native state mass spectrometry to characterise complex biomolecules and their interactions including for contemporary therapeutic modalities such as targeted protein degradation, fragment-based drug discovery and RNA targeting. Her research is defined by the application of chemistry expertise to address complex questions across biology. She was appointed as a Fellow of the Royal Australian Chemical Institute (RACI) in 2017 and was Chair of the RACI Medicinal Chemistry and Chemical Biology Division 2021-2023. She is the author of more than one hundred publications in the field of medicinal chemistry and chemical biology.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

RSC Medicinal Chemistry is delighted to introduce our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Associate Editor Cynthia Dowd (George Washington University, USA). Take a look at which articles she chose and why.

Cynthia Dowd’s favourite articles

Rational design of small-sized peptidomimetic inhibitors disrupting protein–protein interaction Junyuan Wang, Ping Zheng, Jianqiang Yu, Xiuyan Yang* and Jian Zhang* RSC Med. Chem., 2024, 15, 2212-2225

Cynthia’s comments:

“Disruption of protein-protein interfaces could be seen as the ‘holy grail’ of drug discovery. Indeed, much of biology and biochemistry is mediated through such protein-protein interactions (PPI). In this review, Wang et al. describe the most recent strategies for the design and development of molecules aimed at disrupting PPI. These strategies could be used by the field across a variety of protein partners.”

Replacement of nitro function by free boronic acid in non-steroidal anti-androgens (Open Access) Petr Šlechta, Roman Viták, Pavel Bárta, Kateřina Koucká, Monika Berková, Diana Žďárová, Andrea Petríková, Jiří Kuneš, Vladimír Kubíček, Martin Doležal, Radek Kučera and Marta Kučerová-Chlupáčová* RSC Med. Chem., 2024, 15, 4018-4038

Cynthia’s comments:

“Since the clinical introduction and success of bortezomib, the investigation of boron and boronic acids in medicinal chemistry has increased. The work in this paper expands on the exploration of the boronic acid as an isostere of the nitro group within a set of antiandrogens. The authors investigate not only in vitro activity, but also the toxicity of the resulting molecules, enabling expansion of nitro-group isosterism that might be applicable to other compound classes.”

Small molecule antipathogenic agents against Staphylococcus aureus infections Paulo Anastácio Furtado Pacheco, Charlotte Uldahl Jansen, Morten Rybtke, Tim Tolker-Nielsen and Katrine Qvortrup* RSC Med. Chem., 2025, Advance Article

Cynthia’s comments:

“Many anti-infective drug discovery efforts have been focused on inhibition of a function that is essential to the pathogen. In this review, the authors report on work aimed at targeting bacterial virulence factors as a way of controlling the organism. Termed “antipathogenic drugs”, these methods may result in less drug resistance compared with more traditional antibacterial drug discovery.”

Meet the Editor

Cynthia Dowd, RSC Medicinal Chemistry Associate Editor George Washington University, USA Dr. Cynthia Dowd is a Professor of Chemistry at George Washington University.  She obtained a BA in Chemistry from the University of Virginia and a PhD in Medicinal Chemistry from Virginia Commonwealth University.  Following a postdoc at the University of Pennsylvania, Cindy was an intramural scientist at the National Institutes of Health (NIH).  There, she led a small molecule chemistry group to discover novel agents against tuberculosis. In 2007, she began her independent career at GWU where her research is focused on the design and synthesis of novel anti-infective therapies, directed primarily against tuberculosis, malaria and the ESKAPE pathogens.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

RSC Medicinal Chemistry is delighted to introduce our Editor’s choice collection

This collection showcases some of the best articles published in the journal, handpicked by our Associate Editors and Editorial Board members.

Below we have a selection of recent RSC Medicinal Chemistry articles chosen by Associate Editor Jian Zhang (Shanghai Jiao Tong University School of Medicine, China). Take a look at which articles he chose and why.

Jian Zhang’s favourite articles

Rosavin improves insulin resistance and alleviates hepatic and kidney damage via modulating the cGAS-STING pathway and autophagy signaling in HFD/STZ-induced T2DM animals Hebatallah S. Ali*, Hiba S. Al-Amodi, Shaimaa Hamady, Marian M. S. Roushdy, Amany Helmy Hasanin, Ghada Ellithy, Rasha A. Elmansy, Hagir H. T. Ahmed, Enshrah M. E. Ahmed, Doaa M. A. Elzoghby, Hala F. M. Kamel, Ghida Hassan, Hind A. ELsawi, Laila M. Farid, Mariam B. Abouelkhair, Eman K. Habib, Mohamed Esawie, Heba Fikry, Lobna A. Saleh and Marwa Matboli* RSC Med. Chem., 2024, 15, 2098-2113

Jian’s comments:

“This research has found that rosavin can improve insulin resistance and alleviate liver and kidney damage, providing experimental evidence for the application of rosavin in the treatment of diabetes. It provides a direction for the development of new diabetes treatment drugs or strategies and has potential clinical application value.”

Exploiting spirooxindoles for dual DNA targeting/CDK2 inhibition and simultaneous mitigation of oxidative stress towards selective NSCLC therapy; synthesis, evaluation, and molecular modelling studies Mohammad Shahidul Islam, Refaah M. Al-Jassas, Abdullah Mohammed Al-Majid*, Matti Haukka, Mohamed S. Nafie, Marwa M. Abu-Serie, Mohamed Teleb*, Amira El-Yazbi, Abdul Majeed Abdullah Alayyaf, Assem Barakat* and Marwa M. Shaaban* RSC Med. Chem., 2024,15, 2937-2958

Jian’s comments:

“Ligand-capped oxindole compounds were designed and studied, which can simultaneously achieve dual DNA targeting, CDK2 inhibition, and reduction of oxidative stress. This provides a multi-targeted treatment strategy for non-small cell lung cancer (NSCLC), potentially overcoming the limitations of single-target treatment and improving the therapeutic effect.”

The synthesis and bioactivities of ROCK2 inhibitors with 1,2-dithiolan-3-yl motif Ruolin Cao, Fangyu Du, Zhiqiang Liu, Pengcheng Cai, Minggang Qi, Wei Xiao*, Xuefei Bao* and Guoliang Chen* RSC Med. Chem., 2024, 15, 3576-3596

Jian’s comments:

“This paper designed and studied the macrocyclic oxindole compounds, which could simultaneously achieve dual DNA target design and synthesized a ROCK2 inhibitor with a 1, 2-dithia-cyclopentane-3-yl motif. The introduction of this specific structure may provide new ideas and structural templates for the design of ROCK2 inhibitors and enrich the chemical structure diversity of ROCK2 inhibitors.”

Meet the Editor

Jian Zhang, RSC Medicinal Chemistry Associate Editor Shanghai Jiao Tong University School of Medicine, China Jian Zhang is a Distinguished Professor and Head of the Medicinal Chemistry & Bioinformatics Center at Shanghai Jiaotong University School of Medicine. In addition, he is also Dean of the School of Pharmacy at Ningxia Medical University, a member of the Academic Degrees Committee of the State Council in China, and founder of Nutshell Therapeutics. In the last decade, his research has been concerned with drug design, medicinal chemistry and chemical biology, especially target identification and first-in-class allosteric drug discovery.

We hope you enjoyed reading these articles. Keep an eye out on our collection webpage for more of our Editors’ favourite articles.

This article describes the structure-guided optimisation of a screening hit against the pro-survival protein BCL-X_L, which is often overexpressed in solid tumors and results in malignant tumor cells showing resistance to anticancer treatments.

Structure-guided design of a selective BCL-X_L inhibitor
Guillaume Lessene, Peter E Czabotar, Brad E Sleebs, Kerry Zobel, Kym N Lowes, Jerry M Adams, Jonathan B Baell, Peter M Colman, Kurt Deshayes, Wayne J Fairbrother, John A Flygare, Paul Gibbons, Wilhelmus J A Kersten, Sanji Kulasegaram, Rebecca M Moss, John P Parisot, Brian J Smith, Ian P Street, Hong Yang, David C S Huang and Keith G Watson
Nature Chemical Biology, 9, 390–397, (2013)

Editors’ Choice articles are articles identified as being of high potential interest to medicinal chemists, selected from the wider literature by members of the Editorial Board.

In this commentary article, Mark Bunnage and colleagues propose that by developing a ‘chemical probe tool kit’, chemical biology can play a more important part in seeking out potentially relevant targets.

Target validation using chemical probes
Mark E Bunnage, Eugene L Piatnitski Chekler & Lyn H Jones
Nature Chemical Biology, 9, 195–199 (2013)

Editors’ Choice articles are articles identified as being of high potential interest to medicinal chemists, selected from the wider literature by members of the Editorial Board.