Background:

HC-067047 is a potent and selective TRPV4 antagonist and reversibly inhibits currents through the human, rat, and mouse TRPV4 orthologs with IC50 values of 48 nM, 133 nM, and 17 nM, respectively[1].

HC-067047 (1 μM; 24 hours; HEI-OC1 cells) treatment significantly decreases mRNA expression in high glucose cultured HEI-OC1 cells[2].HC-067047 (1 μM; 24 hours; HEI-OC1 cells) treatment significantly decreases the expression of TRPV4 protein[2].HC-067047 (1 μM; 48 hours; HEI-OC1 cells) treatment inhibits cell proliferation[2].HC-067047 (1 μM; 48 hours; HEI-OC1 cells) treatment promotes cell apoptosis[2].

HC-067047 (0-50 mg/kg; intraperitoneal injection; for 30 minutes; cyclophosphamide-treated WT and Trpv4?/? mice, and naive WT mice) treatment increases functional bladder capacity and reduces micturition frequency in WT mice with cystitis. HC-067047 do not affect bladder function in Trpv4?/? mice[1].

参考文献:
[1]. Everaerts W et al. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19084-9.
[2]. Xing Y, et al. Decreased Expression of TRPV4 Channels in HEI-OC1 Cells Induced by High Glucose Is Associated with Hearing Impairment. Yonsei Med J. 2018 Nov;59(9):1131-1137.