883031-03-6 Usage
Description
2-Methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide, also known as HC-067047, is a potent reversible and selective transient receptor potential cation channel subfamily V member 4 (TRPV4) blocker. It exhibits high selectivity and potency for TRPV4 channels, with IC50 values of 17, 48, and 133 nM for mouse, human, and rat TRPV4, respectively. HC-067047 also inhibits the endogenous TRPV4-mediated response to 4α-PDH (IC50 = 22 nM) and shows selectivity over other TRP channels such as TRPV1, TRPV2, TRPV3, and TRPM8.
Uses
Used in Pharmaceutical Research:
HC-067047 is used as a TRPV4 inhibitor for studying its effects on organoid formation and proliferation in human endometrial tissues. This helps researchers understand the role of TRPV4 channels in endometrial function and their potential as therapeutic targets for related conditions.
Used in Neurological Research:
HC-067047 is employed to determine its effects on neuronal survival after intracerebral hemorrhage (ICH). This application aids in investigating the role of TRPV4 channels in neuroprotection and the potential of HC-067047 as a treatment for ICH-induced brain injury.
Used in Cellular Signaling Studies:
HC-067047 is utilized to study its effects on TRPV4 regulation of angiotensin II receptor type 1 (AT1R) task, phosphorylation, and β-arrestin recruitment in choroid plexus. This research helps elucidate the complex interactions between TRPV4 channels and other signaling pathways, which may have implications for various physiological and pathological processes.
Used in Preclinical Models:
HC-067047 increases functional bladder capacity and reduces micturition frequency in mice and rats with cystitis, making it a potential therapeutic agent for urinary disorders. Additionally, it inhibits brain edema in middle cerebral artery occlusion mice, suggesting its potential use in treating cerebral edema and related conditions. Furthermore, HC-067047 induces an increase in core body temperature accompanied by increased oxygen consumption in Wistar rats, indicating its potential role in thermoregulation and metabolic studies.
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
Check Digit Verification of cas no
The CAS Registry Mumber 883031-03-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,8,3,0,3 and 1 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 883031-03:
(8*8)+(7*8)+(6*3)+(5*0)+(4*3)+(3*1)+(2*0)+(1*3)=156
156 % 10 = 6
So 883031-03-6 is a valid CAS Registry Number.
883031-03-6Relevant articles and documents
COMPOUNDS WITH TRPV4 ACTIVITY, COMPOSITIONS AND ASSOCIATED METHODS THEREOF
-
Paragraph 0142; 0146; 0147, (2013/11/19)
Compounds, compositions and methods useful for treating ocular diseases are provided. In particular, antagonists of TRPV4, their synthesis, pharmaceutical compositions thereof and methods of treating ocular diseases such as glaucoma, are disclosed.
