Casein Kinase inhibitor A51

Biorbyt

Casein Kinase inhibitor A51 [2079068-74-7]

10

2079068-74-7

Research Use Only

C18H25ClN6

360.89

Casein Kinase inhibitor A51 (CKIalpha inhibitor A51) is a novel pan-specific CKI (CSNK1) inhibitor (Kd=0.5-20 nM, CKIalpha Kd=5.3 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 CKIalpha 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.

[C@@H](NC1=NC=C(Cl)C(C2=C(CC3CC3)N(C)N=C2)=N1)1CC[C@H](N)CC1

12352200