Casein Kinase inhibitor A86

Biological Activity

Casein Kinase inhibitor A86 is a potent and orally active casein kinase 1α (CK1α) inhibitor. Casein Kinase inhibitor A86 also inhibits of CDK7 (TFIIH) and CDK9 (P-TEFb). Casein Kinase inhibitor A861 induces leukemia cell apoptosis, and has potent anti-leukemic activities[1]. Casein Kinase inhibitor A86 is highly effective in inducing leukemia cell apoptosis at 160 nM or lower, mostly in correlation to their capacity to stabilize p53[1].Casein Kinase inhibitor A86 (0.08-2 μM; 6.5 hours) abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1. Casein Kinase inhibitor A86 induces a marked reduction in mRNA expression of MYC and MDM2, yet upregulates the expression of the Wnt targets AXIN2 and CCND1 (Cyclin D1)[1]. Pharmacokinetic studies of the inhibitor Casein Kinase inhibitor A86 at 20 mg/kg reveal rapid oral absorption with a Tmax of 0.2-0.5 hr, Cmax of 1115 ng/mL, T1/2 of 4.3 hr, and area under the curve (AUC) values of 2606 (ng*hr/mL)[1].

References

[1]. Waleed Minzel, et al. Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell. 2018 Sep 20;175(1):171-185.e25.