(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。
| 生物活性 | (S,R)-WTIDH1 Inhibitor2 (GSK321) is a potent, selective mutantIDH1inhibitor withIC50values of 2.9, 3.8, 4.6 and 46 nM for R132G, R132C, R132H and WTIDH1, respectively, and >100-fold selectivity over IDH2. (S,R)-WTIDH1 Inhibitor2 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)-WTIDH1 Inhibitor2 can be used for research of acute myeloid leukemia (AML) and other cancers[1]. |
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体外研究
(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 EC50value 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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体内研究
(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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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