GSK2193874

• CAT Number: I007081
• CAS Number: 1336960-13-4
• Molecular Formula: C37H38BrF3N4O
• Molecular Weight: 691.637
• Purity: ≥95%
• Target: TRP Channel
• Solubility: Soluble in DMSO
• Storage: Store at +4C
• IUPAC Name: 7-bromo-N-(1-phenylcyclopropyl)-3-[(4-piperidin-1-ylpiperidin-1-yl)methyl]-2-[3-(trifluoromethyl)phenyl]quinoline-4-carboxamide
• InChI: InChI=1S/C37H38BrF3N4O/c38-28-12-13-30-32(23-28)42-34(25-8-7-11-27(22-25)37(39,40)41)31(24-44-20-14-29(15-21-44)45-18-5-2-6-19-45)33(30)35(46)43-36(16-17-36)26-9-3-1-4-10-26/h1,3-4,7-13,22-23,29H,2,5-6,14-21,24H2,(H,43,46)
• InChIKey: UIVOZBSCHXCGPS-UHFFFAOYSA-N
• SMILES: C1CCN(CC1)C2CCN(CC2)CC3=C(N=C4C=C(C=CC4=C3C(=O)NC5(CC5)C6=CC=CC=C6)Br)C7=CC(=CC=C7)C(F)(F)F

GSK2193874 (CAT: I007081) is a potent antagonist of TRPV4 (transient receptor potential vanilloid 4) channels. It effectively blocks the influx of calcium induced by the TRPV4 agonist GSK634775, demonstrating IC50 values of 2, 5, and 40 nM. GSK2193874 exhibits selectivity for TRPV4 over a wide range of other human receptors, channels, and enzymes, making it a valuable tool for studying the function and pharmacology of TRPV4 channels. TRPV4 channels are involved in various physiological processes, including osmoregulation, mechanotransduction, and pain perception. The selective antagonism of TRPV4 by GSK2193874 holds promise for therapeutic applications in conditions related to TRPV4 channel dysfunction.

Reference

1:Respir Physiol Neurobiol. 2017 Feb;236:1-4. doi: 10.1016/j.resp.2016.10.010. Epub 2016 Oct 29. TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli.Buday T,Kovacikova L,Ruzinak R,Plevkova J, PMID: 27989888 DOI: 10.1016/j.resp.2016.10.010 Abstract: Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900). Cough response to all tested aerosols was significantly higher than to saline. Pre-treatment with GSK300 did not influence response to osmotic stimuli – only reduced cough to citric acid. GSK900 reduced cough response to hypotonic stimuli and citric acid. TRPV4 mediated activation of airway afferents does not seem to be the exclusive mechanism responsible for cough to osmotic stimuli.Copyright © 2016 Elsevier B.V. All rights reserved.