molecules of the year

The Kronos CDK9 inhibitor, KB-0742, is an ultraselective inhibitor of cyclin-dependent kinase CDK9. The CDK family of kinases have been pursued as cancer drug targets for decades, but family selectivity within the highly conserved kinase family has made it difficult to identify highly selective molecules, resulting in less than ideal tolerability. The molecule has a remarkably efficient, simple structure, rare among selective kinase inhibitors. The nearest off-targets are CDK13 and CDK2 with >60x selectivity, and it is selective against all other CDKs with >200x selectivity (including CDKs 1, 7, 4, and 6). It is currently in Ph. I for MYC-amplified solid tumors.Kronos published the discovery story and preclinical evaluation of this selective CDK9 inhibitor in Cell Chemical Biology in early…