CDK8-IN-20 (Compound 67j) is a highly selective and potent type I CDK8 inhibitor with oral bioavailability, exhibiting an IC50 value of 70.5 nM. The IC50 values for its action on homologous kinases CDK19, CDK7, and CDK9 are 147.8, 726.9, and 217.4 nM, respectively. CDK8-IN-20 effectively inhibits the proliferation of HCT-116, HT-29, and SW-480 cells with IC50 values of 5.9, 17.93, and 9.52 μM, respectively, while demonstrating low cytotoxicity toward normal gastric mucosal epithelial cells (GES-1) with an IC50 greater than 100 μM. It disrupts the Wnt/β-catenin pathway, downregulating β-catenin, Cyclin D1, and c-Myc expression. Additionally, CDK8-IN-20 induces reactive oxygen species (ROS) production and leads to G2/M phase and S phase cell cycle arrest. This compound is applicable in cancer research, such as colorectal cancer.

CDK8:70.5 nM