BTX-A51

BTX-A51 (Casein Kinase inhibitor A51) is a potent and orally active casein kinase 1α (CK1α) inhibitor. BTX-A51 induces leukemia cell apoptosis, and has potent anti-leukemic activities^[1]. In Vitro:Similar to CKIα depletion, BTX-A51 (0.05-3.2 μM; 18 hours) treatment of RKO cells abolished most of the Ser45 phosphorylation signal and the consecutive GSK3 phosphorylation cascade resulting in stabilization of β-catenin^[1].
BTX-A51 is highly effective in inducing leukemia cell apoptosis at 160 nM or lower, mostly in correlation to their capacity to stabilize p53^[1].
BTX-A51 (0.08-2 μM; 6.5 hours) abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1. BTX-A51 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].
In Vivo:Oral treatment is initiated at 8 days (BTX-A51; 5 mg/kg/day) after leukemia cell inoculation, at which the percentage of leukemia cells in the BM is more than 1.5% of all cells. all A51-treated mice have normal organ morphology and histology and normal blood counts^[1].
Pharmacokinetic studies of the inhibitor BTX-A51 at 20 mg/kg reveal rapid oral absorption with a T_max of 0.5-2 hr, C_max of 1060 ng/mL, T_1/2 of 2.5 hr, and area under the curve (AUC) values of 3680 (ng*hr/mL)^[1].