In vitro: CX-6258 shows antiproliferative activity against a panel of human cancer cell lines with IC50 of 0.02-3.7 μM, mostly sensitive to acute leukemia cell lines. Combinations of CX-6258 with doxorubicin (10:1 molar ratio) and CX-6258 with paclitaxel (100:1 molar ratio) produces synergistic cell killing with combination index (CI50) values equal to 0.4 and 0.56, respectively. 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. In vivo: CX-6258 exhibits dose dependent efficacy in suppressing tumor growth in mice carrying MV-4-11 xenografts, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||57 mg/mL warmed in DMSO|
Discovery of CX-6258. A Potent, Selective, and Orally Efficacious pan-Pim Kinases Inhibitor
Haddach M, et al. ACS Med Chem Lett 2011 Dec 27;3(2):135-9. PMID: 24900437.
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|TCS PIM-1 1
TCS PIM-1 1 is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s > 20,000 nM).
CX-6258 is a potent, orally efficacious Pim 1/2/3 kinase(IC50=5 nM/25 nM/16 nM) inhibitor with excellent biochemical potency and kinase selectivity.
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