GSK 2837808A

GSK2837808A is a selective inhibitor of lactate dehydrogenase A (LDHA) with IC₅₀ of 2.6 nM and 43 nM for hLDHA and hLDHB^[1].

GSK2837808A(10 µM;24-72h) blocked the effect of Centromere protein N (CENP-N) overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance^[2]. GSK2837808A(0, 5, 10, 20 µM) reversed the occurrence of low ratio of ATP/AMP, high level of Adenosine Monophosphate-activated Protein Kinase (AMPK) activation, disturbed HAS2 synthesis and hyaluronic acid (HA) production by inhibiting LDHA in TMJ osteoarthritis synovial fibroblasts (TMJOA SFs)^[3].

GSK2837808A(6 mg/kg/day;p.o;4weeks) treatment, KPC and CAF tumor weight and tumor volume decreased significantly, tumor lactate to lactate: pyruvate ratio decreased significantly, and apoptosis of tumor cells increased in mice^[4].

References:
[1]. Billiard J, Dennison JB, et,al. 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]. Qi CL, Huang ML, et,al. The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis. J Exp Clin Cancer Res. 2021 Dec 10;40(1):390. doi: 10.1186/s13046-021-02191-3. PMID: 34893086; PMCID: PMC8662847.
[3]. Li HM, Guo HL, et,al. Inhibition of glycolysis by targeting lactate dehydrogenase A facilitates hyaluronan synthase 2 synthesis in synovial fibroblasts of temporomandibular joint osteoarthritis. Bone. 2020 Dec;141:115584. doi: 10.1016/j.bone.2020.115584. Epub 2020 Aug 11. PMID: 32795674.
[4].Gupta VK, Sharma NS, et,al. Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer. Cancer Res. 2021 Aug 1;81(15):4001-4013. doi: 10.1158/0008-5472.CAN-20-2562. Epub 2021 May 14. PMID: 33990397; PMCID: PMC8338764.