Casein Kinase inhibitor A86 is a highly effective and orally bioavailable inhibitor of casein kinase 1α (CK1α) and also inhibits CDK7 (TFIIH) and CDK9 (P-TEFb). It induces apoptosis in leukemia cells, exhibiting substantial anti-leukemic effects.

CDK7:0.31 nM (Kd), CDK9:5.4 nM (Kd)

Casein Kinase Inhibitor A86 effectively induces apoptosis in leukemia cells at concentrations of 160 nM or lower, largely due to its ability to stabilize p53[1]. At dosages ranging from 0.08 to 2 μM over 6.5 hours, it significantly suppresses the expression of oncogenes MYC, MDM2, and the anti-apoptotic MCL1, while also markedly decreasing the mRNA levels of MYC and MDM2. Conversely, it enhances the expression of Wnt pathway targets AXIN2 and CCND1 (Cyclin D1)[1]. Notably, in MV4-11 cells treated with 0.08 μM, 0.6 μM, and 2 μM for 6.5 hours, Casein Kinase Inhibitor A86 abolishes the expression of MYC, MDM2, and MCL1, demonstrating its potent anticancer activity[1].

Pharmacokinetic analysis of Casein Kinase inhibitor A86 administered at 20 mg/kg demonstrates swift oral absorption, characterized by a T max range of 0.2-0.5 hours, a peak concentration (C max) of 1115 ng/mL, a half-life (T 1/2) of 4.3 hours, and area under the curve (AUC) values of 2606 ng*hr/mL[1].