(R,R)-GSK321 is a mutant R132H IDH1 inhibitor with an IC50 value of 120nM. (R,R)-GSK321 is an isomer of GSK321 with some wild type cross reactivity[1].
In vitro, A-498 cells treated with 0.1-3μM (R,R)-GSK321 in the presence of 2mM 1-¹³C-glutamine for 5 hours, observed a dose-dependent decrease in reductive glutaminolysis[1].
References:
[1] Jakob CG, Upadhyay AK, Donner PL, et al. Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315. J Med Chem. 2018;61(15):6647-6657.
(R,R)-GSK321是一种突变型R132H IDH1抑制剂，IC50值为120nM。(R,R)-GSK321是GSK321的异构体，具有野生型交叉反应性[1]。
体外实验中，在2mM 1-¹³C-谷氨酰胺存在下，用0.1-3μM (R,R)-GSK321处理A-498细胞5小时，观察到还原性谷氨酰胺分解作用呈剂量依赖性下降[1]。