msc2530818

Description: MSC2530818 is novel, potent, selective and orally available small molecule inhibitor of cyclin dependent kinase CDK8 with the IC50 of 2.6 nM. It demonstrates excellent pharmacokinetics and pharmacodynamics including good kinase selectivity, high biochemical and cellular potency, microsomal stability, and reasonable oral bioavailability. The mediator complex-associated cyclin dependent kinase CDK8 regulates beta-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development of colorectal cancer. MSC2530818 was identified in a high-throughput screening campaign and further progressed by structure-based design. MSC2530818 demonstrated suitable potency and selectivity to progress into preclinical in vivo efficacy and safety studies.

References: J Med Chem. 2016 Oct 27; 59(20):9337-9349.