CX-6258 hydrochloride hydrate

CX-6258 hydrochloride hydrate is a potent and kinase selective pan-Pim kinases inhibitor, with IC 50 s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively

In Vitro

CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. CX-6258 treatment (12 mM, 3 h) treatment diminishes steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment results in a significant reduction in NKX3.1 half-life. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MV-4-11 human AML cells. Concentration: 0.1 μM, 1 μM, 10 μM. Incubation Time: 2 hours. Result: Caused dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively.

In Vivo

CX-6258 (50-100 mg/kg; p.o; daily; over a period of 21 days) exhibits robust in vivo efficacy in two Pim kinases driven tumor models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Nude mice, MV-4-11 xenograft models Dosage: 50 mg/kg, 100 mg/kg. Administration: Oral administration; once daily; over a period of 21 days. Result: Exhibited dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI.

IC50& Target:IC50: 5 nM (Pim-1), 25 nM (Pim-2), 16 nM (Pim-3)