GSK321
目录号 : GC67771GSK321 是突变异柠檬酸脱氢酶 1 (IDH1) 酶的有效抑制剂。GSK321 对突变的 IDH1 酶具有高抑制性和选择性。GSK321 可用于急性髓性白血病的研究。
Cas No.:1816331-63-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
GSK321 is a potent inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) enzymes. GSK321 has high inhibitory and selectivity for mutant IDH1 enzymes. GSK321 can be used for the research of acute myeloid leukemia[1][2].
GSK321 has high inhibitory for mutant IDH1 enzymes, with IC50 values of 4.6 nM against R132H, 3.8 nM against R132C and 2.9 nM against R132G, respectively[1].
GSK321 (0, 0.5, 5 μM; 48 h) induces markedly decreased H3K9me2 levels[1].
GSK321 decreases intracellular 2-HG and affects proliferation of primary IDH1 mutant AML cells[1].
GSK321 has inhibition activity for mutant IDH1 that overcomes the pathognomonic differentiation block of AML cells, and induces myeloid differentiation of IDH1 mutant cells at the level of leukemic blasts and more stem-like cells[1].
GSK321 leads to genome-wide DNA cytosine hypomethylation in IDH1-mutant AML cells[1].
Western Blot Analysis[1]
| Cell Line: | HT-1080 cells |
| Concentration: | 0, 0.5, 5 μM |
| Incubation Time: | 48 h |
| Result: | Lead to the reduction of histone H3K9 dimethylation (H3K9me2). |
Cell Proliferation Assay[1]
| Cell Line: | IDH1 mutant AML cells |
| Concentration: | 3 μM |
| Incubation Time: | 15 days |
| Result: | Showed a significant, initial increase in cell numbers (2-fold to 15-fold) in IDH1 mutant AML cells. |
Cell Cycle Analysis[1]
| Cell Line: | IDH1 mutant AML cells |
| Concentration: | |
| Incubation Time: | 7 days |
| Result: | Observed a reproducible and significant decrease in quiescent (G0)-phase cells in R132G IDH1 and R132C IDH1 AML cells. |
[1]. Ujunwa C Okoye-Okafor, et al. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86.
[2]. Stuart Jones, et al. Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells. J Med Chem. 2016 Dec 22;59(24):11120-11137.
| Cas No. | 1816331-63-1 | SDF | Download SDF |
| 分子式 | C28H28FN5O3 | 分子量 | 501.55 |
| 溶解度 | DMSO : 250 mg/mL (498.45 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9938 mL | 9.9691 mL | 19.9382 mL |
| 5 mM | 0.3988 mL | 1.9938 mL | 3.9876 mL |
| 10 mM | 0.1994 mL | 0.9969 mL | 1.9938 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Metabolic reprogramming in the OPA1-deficient cells
Cell Mol Life Sci 2022 Sep 14;79(10):517.PMID:36103091DOI:10.1007/s00018-022-04542-5
OPA1, a dynamin-related GTPase mutated in autosomal dominant optic atrophy, is essential for the fusion of the inner mitochondrial membrane. Although OPA1 deficiency leads to impaired mitochondrial morphology, the role of OPA1 in central carbon metabolism remains unclear. Here, we aim to explore the functional role and metabolic mechanism of OPA1 in cell fitness beyond the control of mitochondrial fusion. We applied [U-13C]glucose and [U-13C]glutamine isotope tracing techniques to OPA1-knockout (OPA1-KO) mouse embryonic fibroblasts (MEFs) compared to OPA1 wild-type (OPA1-WT) controls. Furthermore, the resulting tracing data were integrated by metabolic flux analysis to understand the underlying metabolic mechanism through which OPA1 deficiency reprograms cellular metabolism. OPA1-deficient MEFs were depleted of intracellular citrate, which was consistent with the decreased oxygen consumption rate in these cells with mitochondrial fission that is not balanced by mitochondrial fusion. Whereas oxidative glucose metabolism was impaired, OPA1-deficient cells activated glutamine-dependent reductive carboxylation and subsequently relied on this reductive metabolism to produce cytosolic citrate as a predominant acetyl-CoA source for de novo fatty acid synthesis. Prevention of cytosolic glutamine reductive carboxylation by GSK321, an inhibitor of isocitrate dehydrogenase 1 (IDH1), largely repressed lipid synthesis and blocked cell proliferation in OPA1-deficient MEFs. Our data support that, when glucose oxidation failed to support lipogenesis and proliferation in cells with unbalanced mitochondrial fission, OPA1 deficiency stimulated metabolic anaplerosis into glutamine-dependent reductive carboxylation in an IDH1-mediated manner.