CX-6258 hydrochloride

CX-6258 hydrochloride is a potent and kinase selective pan-Pim kinases inhibitor, with IC50s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> Pim

IC50: 5 nM (Pim-1), 25 nM (Pim-2), 16 nM (Pim-3)[1].

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[1]. CX-6258 treatment (12 mM, 3 h) treatment diminishes steady-state levels of ectopic NKX3.1 in PC3 cells[2]. CX-6258 treatment results in a significant reduction in NKX3.1 half-life[2]. Western Blot Analysis[1] Cell 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.

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[1]. Animal Model: Nude mice, MV-4-11 xenograft models[1] Dosage: 50 mg/kg, 100 mg/kg. Administration: Oral administration; once daily; over a period of 21 days. Result: Exhibitd dose dependent efficacy, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI.

[1]. Mustapha Haddach, Jerome Michaux, Michael K, Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor. ACS Med. Chem. Lett., 2012, 3 (2), pp 135-139.

[2]. Padmanabhan A, Gosc EB, Bieberich CJ. Stabilization of the prostate-specific tumor suppressor NKX3.1 by the oncogenic protein kinase Pim-1 in prostate cancer cells. J Cell Biochem. 2013 May;114(5):1050-7.