HC-067047 (883031-03-6) is a potent reversible and selective TRPV4 antagonist. Active at mouse, human and rat TRPV4, IC50 = 17, 48 and 133 nM respectively. Also inhibits the endogenous TRPV4-mediated response to 4α-PDH (IC50 = 22 nM). Selective for TRPV4 over TRPV1, TRPV2, TRPV3 and TRPM8 channels1. Increases functional bladder capacity and reduces micturition frequency in mice and rats with cystitis1. Inhibits brain edema in middle cerebral artery occlusion mice2. HC-067047 induces an increase in core body temperature accompanied by increased oxygen consumption in Wistar rats3. Active in vivo.
1) Everaerts et al. (2010), Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphoamide-induced cystitis; Proc. Natl. Acad. Sci. USA, 107 19084
2) Jie et al. (2015), Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice; Front. Cell. Neurosci., 9 141
3) Vizin et al. (2015), TRPV4 activates autonomic and behavioural warmth-defence responses in Wistar rats; Acta Physiol. (Oxf.), 214 275