GSK2798745, a clinical candidate, was identified as an inhibitor of the transient receptor potential vanilloid 4 (TRPV4) ion channel with IC50 of 1.8 and 1.6nM for hTRPV4 and rTRPV4, respectively[1].
In vitro, GSK2798745 (0.3-100nM) inhibited TRPV4 channel activation in a dose-dependent manner following 1h treatment in 293T cells transfected with wild-type or mutant TRPV4[2].
In vivo, Treatment with GSK2798745 at a dose of 10mg/kg by twice daily intraperitoneal injections for 17 days can treat skeletal abnormalities caused by persistent activity of the mutant channel in Col2a1-Cre/Trpv4p.R594H mice[2].
References:
[1] Brooks CA, Barton LS, Behm DJ, et al. Discovery of GSK2798745: A Clinical Candidate for Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). ACS Med Chem Lett. 2019;10(8):1228-1233.
[2] Nevarez L, Ismaili TK, Zieba J, et al. Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice. JCI Insight. 2026;11(2):e182439.