GSK321

GSK321 is a potent, selective mutant IDH1 inhibitor with IC₅₀ values of 2.9, 3.8, 4.6 and 46 nM for R132G, R132C, R132H and WT IDH1, respectively, and >100-fold selectivity over IDH2. GSK321 induces decrease in intracellular α-Hydroxyglutaric acid (2-HG) (HY-113038B), abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells. GSK321can be used for research of acute myeloid leukemia (AML) and other cancers^[1]. IC50 & Target:IC50 for mutant IDH1 enzymes: 4.6 nM (R132H), 3.8 nM (R132C), 2.9 nM (R132G)^[1]. In Vitro:GSK321 (0.1-10000 nM; 24 h) inhibits intracellular 2-HG production in HT1080 cells with an EC₅₀ value of 85 nM^[1].
GSK321 (0-5 μM; 48 h; HT1080 fibrosarcoma cells) leads to reduction of histone H3K9 dimethylation (H3K9me2)^[1].
GSK321 (3 μM; 22 d) decreases intracellular 2-HG in a dose-dependent manner (R132G, 0.13-fold; R132C, 0.15-fold; R132H, 0.29-fold)^[1].
GSK321 (3 μM; 15 d) affects proliferation of primary IDH1 mutant AML cells^[1].
GSK321 (3 μM; 9 d) induces differentiation in primary IDH1 mutant AML blasts and immature stem-like cells^[1]. In Vivo:GSK321 (150 mg/kg; i.p.; daily, for 15 d; male CD-1 mice with IDH1 mutant AML xenograft) reduces leukemic blasts in vivo^[1].