| Description |
(S,R)-WT IDH1 Inhibitor 2 (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. (S,R)-WT IDH1 Inhibitor 2 induces decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells. (S,R)-WT IDH1 Inhibitor 2 can be used for research of acute myeloid leukemia (AML) and other cancers[1].
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| Related Catalog |
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| Target |
IC50: 2.9 (R132G), 3.8 (R132C), 4.6 (R132H) and 46 nM (WT IDH1)[1]
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| In Vitro |
(S,R)-WT IDH1 Inhibitor 2 (GSK321; 0.1-10000 nM; 24 h) inhibits intracellular 2-HG production in HT1080 cells with an EC50 value of 85 nM[1]. (S,R)-WT IDH1 Inhibitor 2 (0-5 μM; 48 h; HT1080 fibrosarcoma cells) leads to reduction of histone H3K9 dimethylation (H3K9me2)[1]. (S,R)-WT IDH1 Inhibitor 2 (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]. (S,R)-WT IDH1 Inhibitor 2 (3 μM; 15 d) affects proliferation of primary IDH1 mutant AML cells[1]. (S,R)-WT IDH1 Inhibitor 2 (3 μM; 9 d) induces differentiation in primary IDH1 mutant AML blasts and immature stem-like cells[1]. Cell Viability Assay[1] Cell Line: IDH1 mutant AML cells Concentration: 3 μM Incubation Time: 15 days Result: Increased in cell numbers (2-fold to 15-fold) in IDH1 mutant AML cells. Cell Cycle Analysis[1] Cell Line: IDH1 mutant AML cells Concentration: 3 μM Incubation Time: 15 days Result: Decreased in quiescent (G0)-phase cells and increased in G1-phase in R132G IDH1. Western Blot Analysis[1] Cell Line: HT1080 fibrosarcoma cells Concentration: 0, 0.5 and 5 μM Incubation Time: 48 hours Result: Induced markedly decreased H3K9me2 levels.
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| In Vivo |
(S,R)-WT IDH1 Inhibitor 2 (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]. Animal Model: Male CD-1 mice with IDH1 mutant AML xenograft[1] Dosage: 150 mg/kg Administration: Intraperitoneal injection; daily, for 15 days Result: Decreased in 2HG in IDH1-mutant AML cells. Decreased in the percentage of blast cells (SSClowCD45low/+) and a relative increase in mature lymphoid and granulocytic/monocytic cells.
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| References |
[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.
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