Casein Kinase inhibitor A86

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

酪蛋白激酶抑制剂 A86（CKIα 抑制剂 A86）是一种新型泛特异性 CKI（CSNK1）抑制剂。

Casein Kinase inhibitor A86 (CKIα inhibitor A86) is a novel pan-specific CKI (CSNK1) inhibitor (Kd=1-10 nM, CKIα Kd=9.8 nM) that co-targets the transcriptional kinases CDK7 and CDK9, with hardly inhibition of CDK8, CDK13, CDK11a, CDK11b, and CDK19; target both CDK7 and CDK9 with low nM Kd values; induces leukemia cell apoptosis at <160 nM, in correlation to the capacity to stabilize p53; shows high and selective sensitivity against leukemic CFUs in colony-forming unit (CFU) assay, without effect on normal hematopoietic CFUs; blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, induce apoptosis, abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1; demonstrates therapeutic efficacy with preserved hematopoiesis and leukemia cure potential in AML mouse models.

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.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).Cell Viability AssayCell Line:MV4-11 cells.Concentration:0.08 μM, 0.6 μM, 2 μM Incubation Time:6.5 hours Result:Abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1.

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).

CKIα inhibitor A86

Metabolic Enzyme/Protease

Casein Kinase

Casein Kinase

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2079069-01-3

344.438

C18H25FN6

>98% (HPLC)

In Vitro:?DMSO : 12.5 mg/mL (36.29 mM)

CN1C(=C(C=N1)C2=NC(=NC=C2F)NC3CCC(CC3)N)CC4CC4

(1r,4r)-N1-(4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)-5-fluoropyrimidin-2-yl)cyclohexane-1,4-diamine

(-20℃)

With Ice Pack

≥ 2 years