HC067047 is a selective TRPV4 antagonist with IC50 of 48 nM, 133 nM and 17 nM for human, rat and mouse TRPV4, respectively[1].
In HEI-OC1 cells, HC067047 (1 µM) treatment for 24 hours can significantly reduce the mRNA expression in HEI-OC1 cells cultured in high glucose and reduce the expression of TRPV4 protein. HC067047 (1 µM) treatment for 48 hours can inhibit cell proliferation and promote apoptosis[2].
In WT mice with cystiti, HC067047 (0-50 mg/kg; intraperitoneal injection; for 30 minutes) treatment increases functional bladder capacity and reduces micturition frequency. HC067047 do not affect bladder function in Trpv4−/− mice[1].
References:
[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, 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, 59(9): 1131-1137.