GSK205 (free base)

GSK205 free base is a potent, selective TRPV4 antagonist with an IC₅₀ of 4.19  μM for inhibiting TRPV4-mediated Ca²⁺ influx^[1][2]. IC50 & Target: IC50: 4.19  μM (TRPV4)^[2] In Vitro: GSK205 (100 μM) potently antagonizes TRPV4 in 3T3-F442A adipocytes, as it effectively blocks the calcium influx caused by TRPV4 agonist^[1].
GSK205 (5 μM; 4 days; T3-F442A adipocytes) treatment results in increases expression of thermogenic genes (Mcp1, Mip1α, Mcp3, Rantes and Vcam, et al.) and is also accompanied by a decrease in the proinflammatory gene program. This shift resembles the gene expression changes seen in TRPV4-deficient adipocytes^[1]. In Vivo: GSK205 (10 mg/kg; intraperitoneal injection; twice daily; for 7 days; for 4 weeks; male C57BL/6J mice) treatment shows significantly increases expression of thermogenic genes such as Ucp1, Pgc1a, Cidea and Cox8b. GSK205 treatment causes a reduced expression of the proinflammatory chemokines, macrophage marker and Tnfa in the EPI fat. GSK205 treatment significantly improves glucose tolerance in diet-induced obese (DIO) mice. There are no apparent sign of sickness or weight loss^[1].
GSK205 has a relatively short half-life of 2 hours in the plasma and adipose tissues^[1].