Casein Kinase inhibitor A86 (CK1α inhibitor A86) is a novel pan-specific CK1 (CSNK1) inhibitor (Kd=1-10 nM, CK1α Kd=9.8 nM) that co-targets the transcriptional kinases CDK7 and CDK9, with hardly inhibition of CDK8, CDK13, CDK11a, CDK11b, and CDK19.
Casein Kinase inhibitor A86 (CK1α inhibitor A86) is a novel pan-specific CK1 (CSNK1) inhibitor (Kd=1-10 nM, CK1α Kd=9.8 nM) that co-targets the transcriptional kinases CDK7 and CDK9, with hardly inhibition of CDK8, CDK13, CDK11a, CDK11b, and CDK19.
Casein Kinase inhibitor A86 targets both CDK7 and CDK9 with low nM Kd values; induces leukemia cell apoptosis at <160 nM, in correlation to the capacity to stabilize p53.
Casein Kinase inhibitor A86 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, deprives leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, induce apoptosis, abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1.
Casein Kinase inhibitor A86 demonstrates therapeutic efficacy with preserved hematopoiesis and leukemia cure potential in AML mouse models.
