Description
HC-067047 (883031-03-6) is a potent reversible and selective TRPV4 blocker. 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 channels.1 Increases functional bladder capacity and reduces micturition frequency in mice and rats with cystitis.1 Inhibits brain edema in middle cerebral artery occlusion mice.2 HC-067047 induces an increase in core body temperature accompanied by increased oxygen consumption in Wistar rats.3?Active?in vivo.
Uses
HC-067047?has been used as a transient receptor potential cation channel subfamily V member 4 (TRPV4)?inhibitor:
- to study its effects on organoid formation and proliferation in human endometrial tissues
- to determine its effects on neuronal survival after intracerebral hemorrhage (ICH)
- to study its effects on TRPV4 regulation of angiotensin II receptor type 1 (AT1R) task, phosphorylation and β-arrestin recruitment in choroid plexus
Biochem/physiol Actions
HC-067047 is a potent, selective inhibitor of hTRPV4. The compound inhibits human, rat and mouse TRPV4 with IC50 values of 48, 133 and 17 nM, respectively. HC-067047 does not inhibit other TRPV isoforms at concentrations up to 5 μM. HC-067047 inhibits hERG channel and the menthol receptor TRPM8 with IC50 values of 370 and 780 nM, respectively.
References
1) Everaerts?et al. (2010), Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-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
![2-Methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide Structure](https://www.chemicalbook.com/CAS/GIF/883031-03-6.gif)
