CCT251545 analog is a potent and selective CDK8/19 inhibitor (IC50: 5.1 nM and 5.6 nM, respectively). Mediator complex-associated kinases CDK8 and CDK19 are involved in the regulation of multiple transcription pathways. CDK8 plays as an oncogene in gastric and colorectal cancers through the activation of WNT signaling.

In SW620 human colorectal carcinoma cells harbouring activating APC-mutation, Compound 51 inhibited phospho-STAT1SER727 ( IC50 :17.9 nM). It is a biomarker of CDK8 inhibition [1].

In vivo mouse and rat PK experiments, The compound demonstrated medium in vivo clearance and Vd but low bioavailability in mice. In an SW620 colorectal carcinoma human tumor xenograft model, Compound 51 (5 mg/kg p.o. dose) inhibited phospho-STAT1SER727 in a time-dependent way. Compound 51 is an advanced chemical tool to further explore the efficacy, safety, and tolerability of dual CDK8/19 ligands [1].