Background:

GSK864 is an isocitrate dehydrogenase 1 (IDH1) mutant inhibitor; inhibits IDH1 mutants R132C, R132H, and R132G with IC50 values of 8.8, 15.2 and 16.6 nM.

GSK864 inhibits 2-HG production in R132C IDH1 mutant HT1080 fibrosarcoma cells with an EC50 of 320 nM by LCMS/MS analysis[1].

Following intraperitoneal (IP) administration in CD-1 mice, significant concentrations of GSK864 are maintained in peripheral blood samples of mice for up to 24 hours. Analysis of BM cells for expression of markers of early differentiation reveals slightly increased numbers of huCD45+ CD38+ cells in R132C or R132H IDH1 mutant engrafted mice treated with GSK864[1].

参考文献:
[1]. Okoye-Okafor UC, et al. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86.