GSK2837808A

GSK2837808A is a potent and selective lactate dehydrogenase A (LDHA) inhibitor with IC₅₀s of 2.6 and 43 nM for hLDHA and hLDHB, respectively. IC50 & Target: IC50: 2.6 nM (hLDHA), 43 nM (hLDHB)^[1] In Vitro: GSK2837808A rapidly and profoundly inhibits lactate production rates in multiple cancer cell lines including hepatocellular and breast carcinomas. The potency of GSK2837808A across 30 cancer cell lines with different LDHA and LDHB expression levels ranges from 400 nM to no effect (EC₅₀ reported as 30 μM). GSK2837808A potency does not correlate with LDHA, LDHB, or the total LDH expression levels. GSK2837808A inhibits lactate production in hypoxia but at higher concentrations than in normoxia (EC₅₀=10 μM). It also reduces ECAR with EC₅₀=10 μM. LDH inhibition by GSK2837808A alters multiple metabolic pathways in Snu398 cells^[1]. In Vivo: Clearance following IV infusion of GSK2837808A at 0.25 mg/kg is shown to be 69 mL/minute/kg in rats, which exceeds the animal liver blood flow. Oral dosing of GSK2837808A at 50 mg/kg in rats or 100 mg/kg in mice results in blood compound levels at or below the detection limit of 2.5 ng/mL^[1].