GSK2837808A

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Chemical Structure| 1445879-21-9 同义名 : -
CAS号 : 1445879-21-9
货号 : A723653
分子式 : C31H25F2N5O7S
纯度 : 98%
分子量 : 649.62
MDL号 : MFCD28133406
存储条件：

Pure form Keep in dark place, inert atmosphere, room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Lactate dehydrogenase (LDH) is an essential metabolic enzyme that catalyzes the interconversion of pyruvate and lactate using NADH/NAD(+) as a co-substrate[2]. Lactate dehydrogenase A (LDHA) is a critical metabolic enzyme belonging to a family of 2-hydroxy acid oxidoreductases that plays a key role in anaerobic metabolism in the cells. In hypoxia condition, the overexpression of LDHA shifts the metabolic pathway of ATP synthesis from oxidative phosphorylation to aerobic glycolysis and the hypoxia condition is a common phenomenon occurred in the microenvironment of tumor cells[3]. GSK2837808A is a potent and selective inhibitor of lactate dehydrogenase A (LDHA) (IC50s: 1.9 and 14 nM for LDHA and LDHB, respectively). GSK2837808A inhibits lactate production in hypoxia but at higher concentrations than in normoxia (EC50=10 μM). It also reduces ECAR (EC50=10 μM). LDH inhibition by GSK2837808A alters multiple metabolic pathways in Snu398 cells. GSK2837808A rapidly and profoundly inhibits lactate production rates in multiple cancer cell lines including hepatocellular and breast carcinomas. GSK2837808A potency does not correlate with LDHA, LDHB, or the total LDH expression levels. The potency of GSK2837808A across 30 cancer cell lines with different LDHA and LDHB expression levels range from 400 nM to no effect (EC50 reported as 30 μM). GSK2837808A (p.o.; 50 mg/kg in rats; 100 mg/kg in mice) treatment, causes blood compound levels at or below the detection limit of 2.5 ng/mL. Clearance following IV infusion of GSK2837808A at 0.25 mg/kg is displayed to be 69 mL/minute/kg in rats and it exceeds the animal liver blood flow[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.54mL

0.31mL

0.15mL

7.70mL

1.54mL

0.77mL

15.39mL

3.08mL

1.54mL
参考文献

[1]Billiard J, Dennison JB, Briand J, Annan RS, Chai D, Colón M, Dodson CS, Gilbert SA, Greshock J, Jing J, Lu H, McSurdy-Freed JE, Orband-Miller LA, Mills GB, Quinn CJ, Schneck JL, Scott GF, Shaw AN, Waitt GM, Wooster RF, Duffy KJ. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab. 2013 Sep 6;1(1):19. doi: 10.1186/2049-3002-1-19. PMID: 24280423; PMCID: PMC4178217.

[2]Subramaniapillai Kolappan,et al. Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms. Acta Crystallogr D Biol Crystallogr. 2015 Feb;71(Pt 2):185-95.

[3]Farzaneh Jafary,et al. Novel Peptide Inhibitors for Lactate Dehydrogenase A (LDHA): A Survey to Inhibit LDHA Activity via Disruption of Protein-Protein Interaction. Sci Rep. 2019 Mar 18;9(1):4686.

[4]Billiard J, et al. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab. 2013 Sep 6;1(1):19.