Themed collection Emerging Investigators

RSC Medicinal Chemistry profiles the contributors to the ‘Emerging Investigators’ themed collection.

Recent literature examples of small molecules reported to modulate a homomeric protein complex at sub-stoichiometric concentrations were selected to discuss implications on drug discovery efforts.

Hydroxypyrone derivatives comprise a versatile class of compounds with massive potential as therapeutic and imaging agents. Their excellent metal chelating properties have been exploited to inhibit metalloenzymes.

This review outlines the current state of research into glycomimetic or drug-like small molecule ligands for the C-type lectin receptors Mincle, Langerin, and DC-SIGN, which have potential applications in vaccine research and anti-infective therapy.

Overview of β-lactam antibiotics and the proteins with which they covalently interact, focusing on penicillin-binding proteins and serine β-lactamases.

Selection methods in generating cell-internalizing nucleic acid aptamer via cell-SELEX technique for applications in diagnostics and therapeutics are discussed. Their challenges, optimization strategies and cellular uptake mechanisms are presented.

Macrocyclization between head, tail or sidechains is a frequently employed strategy to enhance peptide and peptidomimetic stability, selectivity and affinity.

Deep neural networks (DNNs) used for de novo drug design have different architectures and hyperparameters that impact the final output of suggested drug candidates. Herein we review benchmarking platforms that assess the utility and validity of DNNs.

Protease inhibitors of West Nile virus have long suffered from insufficient drug likeness, which has been tackled in latest advancements.

In this review, drug metabolizing human carboxylesterases and fluorescent probes capable of studying their activity in live cells are discussed.

There are remarkably few examples of designing cyclic constraints for peptides which adopt an irregular conformation in their bioactive state. We discuss the design strategies, opportunities and challenges for this underexplored class of inhibitors.

High quality chemical probes and chemistry-based target deconvolution techniques will be crucial to the advancement of phenotypic drug discovery, providing new hope for treatment of diseases with highly complex biology.

Tridecaptins are a re-emerging class of non-ribosomal antibacterial peptides (NRAPs) with potent activity against highly problematic strains of Gram-negative bacteria.

Fighting COVID-19 with high affinity reagents: this review article summarizes the discovery of several classes of (bio) molecules targeting the SARS-CoV-2 spike protein.

Interrogation of the Pathogen Box identified diverse chemical scaffolds against the mycobacterial trehalose transporter.

A series of oleic acid amide derivatives were generated as potential small molecule stimulators of the 20S core particle of the proteasome (20S CP), with the goal of increasing the protein degradation rate via the ubiquitin-independent pathway.

To develop new degrader molecules from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the respective targets.

Synthetic cannabinoid receptor agonists (SCRAs) remain one the most prevalent classes of new psychoactive substances (NPS) worldwide, and examples are generally poorly characterised at the time of first detection.

This work describes the photochemical synthesis of a tetrahydroquinoline library enriched with chemotypes privileged for epigenetic targets and exploring new regions of chemical space.

The physicochemical properties of protein–protein interaction (PPI) modulators vary between those on the market, those in clinical trials, and those in the early drug discovery pipeline.

Cyclic dinucleotide analogues that have sulfur atoms on the furanose rings act as potent and stable STING agonists.

Unique synthetic strategies were developed access to new bedaquiline analogues, leading to the discovery that anti-tubercular activity could be retained following replacement of bedaquiline's quinoline A-ring subunit with pyridine heterocycles.

Starting from a literature KRAS^G12C inhibitor, in this article we show how computational chemistry can help guide the process to a highly optimised tetracyclic series which demonstrates strong tumour regression.

Potent A₃ adenosine receptor antagonists were developed to be conjugated and obtain receptor probes, drug delivery systems, and multitarget or bitopic ligands.

This study underscores privileged interactions for RNA binding small molecules, an emerging focus in drug discovery.