GSK2837808A (CAS: 1445879-21-9)

C₃₁H₂₅F₂N₅O₇S

• Potent and selective cell permeable inhibitor of lactate dehydrogenase A (LDHA) (IC₅₀ values are 2.6 and 43 nM for LDHA and LDHB, respectively). Decreases glycolysis.
• Useful agent for immunometabolism research.
• Exhibits antitumoral activity. Inhibits lactate production in selected cancer cell lines. Reduces glucose uptake and enhances mitochondrial oxygen consumption in Snu398 hepatocellular carcinoma cells. Inhibits proliferation and induces apoptosis in Snu398 cells. Inhibits transcription of histone 2B (H2B) gene in HCT116 and NCM460 cells.
• Lactate dehydrogenase A (LDHA) is an important enzyme involved in fermentative glycolysis, important in tumor initiation and metabolism. Cancer cells rely on increased glycolysis resulting in increased lactate production in addition to aerobic respiration in the mitochondria, even under normal oxygen concentrations (a process known as the Warburg effect). This renders LDHA a promising molecular target for the treatment of various cancers.

1. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells: J. Billiard, et al.; Cancer Metab. 1, 19 (2013)
2. Targeting lactate dehydrogenase-A inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor initiating cells: H. Xie, et al.; Cell Metab. 19, 795 (2014)
3. A guide to immunometabolism for immunologists: L.A. O'Neill, et al.; Nat. Rev. Immunol. 16, 553 (2016)
4. The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis: E. Brighenti, et al.; BBRC 485, 742 (2017)