Casein Kinase Inhibitor A51

Casein kinase inhibitor A51 is an inhibitor of casein kinase 1alpha (CK1alpha). It binds to CK1alpha, CK1delta, and CK1epsilon (Kds = 5.3, 1.8, and 4.4 nM, respectively) and reduces phosphorylation of beta-catenin at serine 45, a site phosphorylated specifically by CK1alpha, when used at a concentration of 1 µM. Casein kinase inhibitor A51 (27 nM) inhibits the proliferation of bone marrow cells isolated from mice with acute myeloid leukemia (AML) driven by the oncogenic fusion protein MLL-AF9. It rapidly increases intratumoral levels of p53 and induces intratumoral apoptosis in a murine model of MLL-AF9-driven AML. Casein kinase inhibitor A51 (5 mg/kg per day) also increases survival and eradicates signs of disease in the same model over five months.. SMILES: CN1N=CC(C2=NC(N[C@H]3CC[C@@H](CC3)N)=NC=C2Cl)=C1CC4CC4. InChi Code: InChI=1S/C18H25ClN6/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)/t12-,13-. InChi Key: RVZJFCNYSSUDCU-JOCQHMNTSA-N