Themed collection Highlights from Industry

PROTACs are an emerging therapeutic approach towards targeted protein degradation. This article examines the leading examples of this modality that are in clinical development through the prism of their physicochemical properties.

The AI retrosynthesis tool AiZynth has made positive impacts on AstraZeneca drug discovery projects. This opinion provides some examples and discusses how AI retrosynthesis fits into pharmaceutical research.

Prospects of novel fourth-generation EGFR-TKIs overcoming C797S-mediated resistance in non-small cell lung cancer.

For an optimal ADC the symbiotic relationship of the three structurally disparate components requires they all function in unison and medicinal chemistry has a huge role to enable this.

This study reports a novel, potent and selective series of ROCK inhibitors based on 8-(azaindolyl)-benzoazepinones identified through a core-hopping strategy.

In silico identification of urease inhibitors based on thiourea, tested to determine IC₅₀ and tested on a catheterised in vitro bladder model, showing efficacy in reducing catheter blockage.

Schematic of proposed mechanism for the treatment of the SLL-1A-16 inhibiting the proliferation in NSCLC.

A torsion angle scan of a virtual library predicts compounds that will afford stable atropisomers identified as potent non-steroidal glucocorticoid receptor modulators.

A pragmatic approach to the discovery of new SARS-COV-2 Mpro inhibitors by combining generative chemistry and computational chemistry approaches.

Tyrosines preferred: tetramers of αvβ6-integrin binding cyclopeptides show more favorable biodistribution (less nonspecific uptake) the more tyrosines they contain, which can not be deduced from the in vitro properties of the peptide monomers.

Flurbiprofen organic selenium compound RY-1-92 has anticancer activity in non-small cell lung cancer by targeting TRPV1 and its downstream MAPK signaling.

Dysregulation of the networking of RNA-binding proteins (RBPs) and RNAs drives many human diseases, including cancers, and the targeting of RNA–protein interactions (RPIs) has emerged as an exciting area of RNA-targeted drug discovery.

A chemical probe (PFI-7) for the Gid4 subunit of the human E3 ligase CTLH degradation complex.

Minimising solvent exposed hydrophobic surface area of payload is identified as a critical design parameter for optimising ADC drug-like properties.

Maleimide is used in antibody–drug conjugate (ADC) generation to attach the drug-linker to the antibody. Maleimide linkers with hydrolysis-enabled maleimides were designed. Corresponding ADCs were made and subjected to thermal stress, and succinimide ring hydrolysis and drug release were measured.

A glucocorticoid receptor modulator (GRM) was conjugated to a mouse anti-TNF antibody using various dipeptide linkers. Impact of dipeptide linkers on ADC physical properties, including solubility, hydrophobicity, and aggregation were evaluated.

Medicinal chemistry efforts starting from the GPCR agonist HTS hit 1 led to the discovery of the potent, selective, brain-penetrating, orally active orexin 2 receptor antagonists 43 that induced sleep in rats.

Compound libraries synthesised and screened against glioma cells built up structure–antiproliferative activity–relationships and informed further design, synthesis and screening, resulting in the discovery of potent CSF-1R inhibitors.

A single O atom at the right position halves liver uptake of αvβ6-integrin targeting RGD peptide trimers. As there is no correlation with polarity proxies, this is interpreted as an emergent phenomenon arising from loss of synergistic interaction.