Themed collection Celebrating the 5th Anniversary of RSC Medicinal Chemistry

This opinion addresses how digitalisation and automation can reduce the synthesis bottleneck in the DMTA cycle. Current automated synthesis & planning, future data-rich integrated platforms, and the medicinal chemist's evolving role are reviewed.

We discuss how native mass spectrometry (nMS) is contributing important analytical insights to guide contemporary drug discovery and development. We focus on diverse modalities including targeted protein degradation (TPD), fragments (FBDD) and mRNA.

A brief review of the history and current status of proximity induced modalities and a look at some of the opportunities for further exploiting these and related modalities, with a particular focus on opportunities beyond degradation.

This review bridges traditional and AI-driven approaches in computational medicinal chemistry, showing how hybrid models, federated learning, and explainable generative AI are reshaping modern drug discovery workflows.

This article presents for the first time a critical analysis of emerging microbiota-sparing innovative therapeutic strategies, target-specificity and molecule-to-medicinal properties.

A general framework for target agnostic screening to exploit chemically induced proximity (CIP): key factors to consider balancing screening and mechanism of action (MoA) deconvolution.

This review highlights recent advances (2020–2024) in 2,4-thiazolidinedione derivatives as anticancer agents, focusing on SAR insights, molecular mechanisms, and their potential to overcome drug resistance.

Literature-curated classical and non-classical bioisosteric replacements from ChEMBL reveal their impact on off-target potency via a KNIME workflow.

Schweinfurthin analogues – SAR, target engagement, MoA.

Glioblastoma multiforme (GBM) is an aggressive and treatment-resistant brain tumor.

A wide variety of biscationic all-alkyl QPC structures were accessed from dimethyl alkyl phosphines, producing a range of atom-economical disinfectant structures that display broad and potent antibacterial activity.

Galectin-1 conjugated to glucose-stabilized gold nanoparticles retains its immunomodulatory function and provides a promising platform for treating autoimmune and chronic inflammatory diseases.

Diversifying the sp³-rich triquinazine core, we prepared four new chiral scaffolds and 26 analogues that reveal how subtle structural changes modulate Janus Kinase activity, yielding a potent JAK1 inhibitor comparable to FDA-approved drugs.

A combinatorial approach integrating BLI and ligand-based NMR for RNA-focused fragment-based drug discovery.

Accessible synthesis of DNA-encoded libraries of up to 3 million-members via sequential amide coupling, validated by CAIX screening. In silico analysis showed lead-like properties, and the libraries are available to support academic drug discovery.

This study identified HSN748 as a potent RET kinase solvent-front mutant inhibitor with a high central nervous system (CNS) permeability.

The first degrader of an ER-resident protein (IRE1α) is described with properties more akin to a molecular glue than a traditional PROTAC, thus challenging the dogma of categorizing degrader modalities based on their physicochemical features.