CDK8/19-IN-2 (compound 12) is a potent inhibitor of cyclin-dependent kinases 8 and 19 (CDK8 and CDK19), exhibiting IC 50 values of 2.08 nM and 2.49 nM, respectively. This orally active compound is applicable in the research of acute myeloid leukemia (AML), breast cancer, and lymphoma.

CDK8/CycC:2.08 nM, CDK19/CycC:2.49 nM

CDK8/19-IN-2 (compound 12) inhibits the proliferation of MV4-11 human AML cells with an IC 50 of 5.719 nM [1]. Additionally, CDK8/19-IN-2 (at concentrations of 0-10 μM) dose-dependently reduces the phosphorylation of STAT1 at serine 727 (p-STAT1 S727) [1].

CDK8/19-IN-2, also known as compound 12, was administered orally at doses of 3-10 mg/kg once daily using gavage in female BALB/c nude mice (6-8 weeks, human AML cell line MV4-11 was subcutaneously inoculated at the right flanks). The compound demonstrated a dose-dependent suppression of tumor growth, achieving tumor growth inhibition (TGI) of 29% and 76% at doses of 3 mg/kg and 10 mg/kg, respectively, without impacting the body weight of the animals [1].