G6PDi-1
(Synonyms: 4-((5-氧代-6,7,8,9-四氢-5H-环庚并[D]嘧啶-2-基)氨基)噻吩-2-甲腈) 目录号 : GC47387An inhibitor of G6PDH
Cas No.:2457232-14-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
G6PDi-1 is a reversible and noncompetitive inhibitor of glucose-6-phosphate dehydrogenase (G6PDH; IC50 = 0.07 µM), the enzyme that converts G6P to 6-phosphogluconolactone using NADP+ as a cofactor in the first step of the pentose phosphate pathway.1 G6PDi-1 (10 and 50 µM) reduces NADPH levels in a variety of cultured cells, including red blood cells and T cells. It decreases colony formation of HCT116 cells when used at concentrations of 20 and 30 µM, an effect that can be rescued by the antioxidant N-acetyl cysteine. G6PDi-1 decreases the production of cytokines induced by phorbol 12-myristate 13-acetate and ionomycin in T cells and prevents PMA-induced oxidative burst in neutrophils.
1.Ghergurovich, J.M., GarcÍa-CaÑaveras, J.C., Wang, J., et al.A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathwayNat. Chem. Biol.16(7)731-739(2020)
| Cas No. | 2457232-14-1 | SDF | |
| 别名 | 4-((5-氧代-6,7,8,9-四氢-5H-环庚并[D]嘧啶-2-基)氨基)噻吩-2-甲腈 | ||
| Canonical SMILES | O=C(CCCC1)C2=C1N=C(NC3=CSC(C#N)=C3)N=C2 | ||
| 分子式 | C14H12N4OS | 分子量 | 284.3 |
| 溶解度 | DMF: 15 mg/ml, DMF:PBS (pH 7.2) (1:4): 0.20 mg/ml, DMSO: 10 mg/ml | 储存条件 | Store at -20°C |
| 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 | 3.5174 mL | 17.5871 mL | 35.1741 mL |
| 5 mM | 0.7035 mL | 3.5174 mL | 7.0348 mL |
| 10 mM | 0.3517 mL | 1.7587 mL | 3.5174 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。
A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway
Nat Chem Biol 2020 Jul;16(7):731-739.PMID:32393898DOI:10.1038/s41589-020-0533-x.
Glucose is catabolized by two fundamental pathways, glycolysis to make ATP and the oxidative pentose phosphate pathway to make reduced nicotinamide adenine dinucleotide phosphate (NADPH). The first step of the oxidative pentose phosphate pathway is catalyzed by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here we develop metabolite reporter and deuterium tracer assays to monitor cellular G6PD activity. Using these, we show that the most widely cited G6PD antagonist, dehydroepiandosterone, does not robustly inhibit G6PD in cells. We then identify a small molecule (G6PDi-1) that more effectively inhibits G6PD. Across a range of cultured cells, G6PDi-1 depletes NADPH most strongly in lymphocytes. In T cells but not macrophages, G6PDi-1 markedly decreases inflammatory cytokine production. In neutrophils, it suppresses respiratory burst. Thus, we provide a cell-active small molecule tool for oxidative pentose phosphate pathway inhibition, and use it to identify G6PD as a pharmacological target for modulating immune response.
β-lapachone-mediated WST1 Reduction as Indicator for the Cytosolic Redox Metabolism of Cultured Primary Astrocytes
Neurochem Res 2023 Jul;48(7):2148-2160.PMID:36811754DOI:10.1007/s11064-023-03878-z.
Electron cycler-mediated extracellular reduction of the water-soluble tetrazolium salt 1 (WST1) is frequently used as tool for the determination of cell viability. We have adapted this method to monitor by determining the extracellular WST1 formazan accumulation the cellular redox metabolism of cultured primary astrocytes via the NAD(P)H-dependent reduction of the electron cycler β-lapachone by cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1). Cultured astrocytes that had been exposed to β-lapachone in concentrations of up to 3 µM remained viable and showed an almost linear extracellular accumulation of WST1 formazan for the first 60 min, while higher concentrations of β-lapachone caused oxidative stress and impaired cell metabolism. β-lapachone-mediated WST1 reduction was inhibited by the NQO1 inhibitors ES936 and dicoumarol in a concentration-dependent manner, with half-maximal inhibition observed at inhibitor concentrations of about 0.3 µM. β-lapachone-mediated WST1 reduction depended strongly on glucose availability, while mitochondrial substrates such as lactate, pyruvate or ketone bodies allowed only residual β-lapachone-mediated WST1 reduction. Accordingly, the mitochondrial respiratory chain inhibitors antimycin A and rotenone hardly affected astrocytic WST1 reduction. Both NADH and NADPH are known to supply electrons for reactions catalysed by cytosolic NQO1. Around 60% of the glucose-dependent β-lapachone-mediated WST1 reduction was prevented by the presence of the glucose-6-phosphate dehydrogenase inhibitor G6PDi-1, while the glyceraldehyde-3-phosphate dehydrogenase inhibitor iodoacetate had only little inhibitory potential. These data suggest that pentose phosphate pathway-generated NADPH, and not glycolysis-derived NADH, is the preferred electron source for cytosolic NQO1-catalysed reductions in cultured astrocytes.