(S,R)-WT IDH1 Inhibitor 2
(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 (AM
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包装价格促销价数量
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10mg￥13350.0010680.00- +
- 货号: ajcf13500
- CAS: 1816272-18-0
- 别名: GSK321
- 分子式: C28H28FN5O3
- 分子量: 501.55
- 纯度: ＞98%
- 溶解度:
- 储存: Store at -20°C
- 库存: 现货
Background
IC50: 2.9 (R132G), 3.8 (R132C), 4.6 (R132H) and 46 nM (WT IDH1)[1]
(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].
(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. |
(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. |
