SR-4835, a small molecule inhibitor currently in phase I clinical trials, targets transcriptional kinases Cdk12 and Cdk13. Biochemical and structural analyses could highlight SR-4835’s selectivity towards Cdk12/Cdk13 over other CMGC kinase family members. We determined the crystal structure of the Cdk12/CycK heterodimer in complex with SR-4835 at 2.7Å resolution, revealing a unique hydrogen bond network mediated by the kinase hinge region. The structural insights provided offer a foundation for optimization and design of reversible Cdk12-specific inhibitors and could facilitate the basis for the development of novel cancer therapeutics. The full study from Max and coworkers is now published in The Journal of Biological Chemistry.