Protein kinases are highly relevant drug targets, yet a significant fraction of the human kinome remains underexplored. Highly potent and selective small-molecule inhibitors used as chemical probes are invaluable tools for enabling the validation and translation of new kinase targets. This review provides an overview and analysis of the high-quality in vivo chemical probes for protein kinases published and deposited at the Chemical Probes Portal in the year 2024. We discuss the design strategies, molecular mechanism of action, details of their use in vitro and in vivo, as well as their application in target (in)validation. We also highlight the importance of wisely selecting chemical probes and encourage best practices in using such tool compounds.

[1-(Ethoxycarbonyl)cyclopropyl] triphenylphosphonium tetrafluoroborate is a limiting key reagent for synthesis of the tricyclic 5,6-dihydropyrimido[5,4-e]indolizine and related scaffolds, which are c...

Abstract. The Chemical Probes Portal (www.chemicalprobes.org) is a free, public resource, based on expert-reviews, that supports the assessment, selection

The FDA’s nod for suzetrigine bolsters confidence in the pharmaceutical industry’s strategy to target sodium channels.

A study assessed 1.2 million biomedical publications and measured the ‘unexpectedness’ of their findings.