|CX-6258 hydrochloride hydratePan-Pim kinases Inhibitor|
Sample solution is provided at 25 µL, 10mM.
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|Cas No.||1353858-99-7||SDF||Download SDF|
|Synonyms||CX6258 hydrochloride hydrate;CX 6258 hydrochloride hydrate|
|Chemical Name||(E)-(3-(5-((5-chloro-2-hydroxy-3H-indol-3-ylidene)methyl)furan-2-yl)phenyl)(4-methyl-1,4-diazepan-1-yl)methanone hydrochloride hydrate|
|Solubility||25℃: DMSO||Storage||Store at -20°C|
IC50 Value: 5 nM (Pim 1); 25 nM (Pim 2); 16 nM (Pim 3)  CX-6258 is a potent, orally efficacious pan-Pim kinases Inhibitor with excellent biochemical potency and kinase selectivity. in vitro: CX-6258 inhibited Flt-3 and Pim-3 (IC50=0.134 and 0.016 uM). At 0.5 uM of CX-6258, only Pim-1, Pim-2, Pim-3, and Flt-3 of the 107 kinases tested were inhibited by more than 80%, showing excellent selectivity. CX-6258 was also shown to be a reversible inhibitor of Pim-1 (Ki=0.005 uM). CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, (13) caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. Pim-1 inhibition using the small molecule inhibitor CX-6258 (12 mM, 3 h) diminishes endogenous NKX3.1 steady state levels in 22RV1 and LNCaP cells. CX-6258 treatment (12 mM, 3 h) treatment diminished steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment resulted in a significant reduction in NKX3.1 half-life. While ectopically expressed NKX3.1 in control cells had a half-life of _90 min, Pim-1 inhibition reduced the half-life to _52 min . in vivo: CX-6258 showed dose-dependent efficacy in mice bearing MV-4-11 xenografts, with 45% and 75% TGI at 50 and 100 mg/kg/day, respectively. Treatment of mice bearing PC3 xenografts with CX-6258 p.o. 50 mg/kg was also well tolerated and produced 51% TGI. Clinical trial: N/A