GSK205

GSK205 is a potent, selective TRPV4 antagonist with an IC50 of 4.19  μM for inhibiting TRPV4-mediated Ca2+ influx[1][2].

IC50: 4.19  μM (TRPV4)[2]

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]. RT-PCR[1] Cell Line: T3-F442A adipocytes Concentration: 5 μM Incubation Time: 4 days Result: Resulted in increased expression of thermogenic genes and is also accompanied by a decrease in the proinflammatory gene program.

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]. Animal Model: Male C57BL/6J mice with high-fat diet[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection; twice daily; for 7 days Result: Caused a reduced expression of the proinflammatory chemokines, macrophage marker and Tnfa in the EPI fat. Significantly improved glucose tolerance in diet-induced obese (DIO) mice.

[1]. Ye L, et al. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell. 2012 Sep 28;151(1):96-110.

[2]. Kanju P, et al. Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain. Sci Rep. 2016 Jun 1;6:26894.