Casein Kinase inhibitor A86

• CAT Number: I044381
• CAS Number: 2079069-01-3
• Molecular Formula: C18H25FN6
• Molecular Weight: 344.43
• Purity: ≥95%
• Synonyms: 4-N-[4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]-5-fluoropyrimidin-2-yl]cyclohexane-1,4-diamine
• InChI: InChI=1S/C18H25FN6/c1-25-16(8-11-2-3-11)14(9-22-25)17-15(19)10-21-18(24-17)23-13-6-4-12(20)5-7-13/h9-13H,2-8,20H2,1H3,(H,21,23,24)
• InChIKey: YSPIHUWHLMNFOV-UHFFFAOYSA-N
• SMILES: CN1C(=C(C=N1)C2=NC(=NC=C2F)NC3CCC(CC3)N)CC4CC4

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].

Reference

[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.
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