(S,R)-WT IDH1 Inhibitor 2 (GSK321) 是一个有效的选择性突变型 IDH1 抑制剂，抑制 R132G、R132C、R132H 和 WT IDH1 的 IC₅₀ 值分别为 2.9、3.8、4.6 和 46 nM，选择性比 IDH2 高出 100 倍。(S,R)-WT IDH1 Inhibitor 2 诱导细胞内 2-HG 减少，髓细胞分化阻滞失效，在白血病母细胞和更不成熟的干细胞水平诱导粒细胞分化。(S,R)-WT IDH1 Inhibitor 2 可用于急性髓系白血病 (AML) 及其他癌症的研究。

(S,R)-WT IDH1 Inhibitor 2 (GSK321) is a potent, selective mutant IDH1 inhibitor with IC 50 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.

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IDH1

(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.
(S,R)-WT IDH1 Inhibitor 2 (0-5 μM; 48 h; HT1080 fibrosarcoma cells) leads to reduction of histone H3K9 dimethylation (H3K9me2).
(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).
(S,R)-WT IDH1 Inhibitor 2 (3 μM; 15 d) affects proliferation of primary IDH1 mutant AML cells.
(S,R)-WT IDH1 Inhibitor 2 (3 μM; 9 d) induces differentiation in primary IDH1 mutant AML blasts and immature stem-like cells. has not independently confirmed the accuracy of these methods. They are for reference only.

(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. has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model:

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[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.