Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype (Cell Chemical Biology)

Olson et al. describe the development and characterization of YKL-5-124, a potent, selective, and covalent CDK7 inhibitor. YKL-5-124 displays biochemical and cellular selectivity for CDK7 over CDK12/13, structurally related kinases. CDK7 inhibition by YKL-5-124 induces a strong cell-cycle arrest and a surprisingly weak effect on RNA Pol II phosphorylation.