Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8 , TRPV , TRPV1 , TRPV3 , TRPV4

Title: Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.

Authors: Zhi-Liang Wei, Margaret T Nguyen, Donogh J R O'Mahony, Alejandra Acevedo, Sheila Zipfel, Qingling Zhang, Luna Liu, Michelle Dourado, Candace Chi, Victor Yip, Jeff Defalco, Amy Gustafson, Daniel E Emerling, Michael G Kelly, John Kincaid, Fabien Vincent, Matthew A J Duncton

Journal, date & volume: Bioorg. Med. Chem. Lett., 2015 Sep 15 , 25, 4011-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26235950

Abstract
Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to rats. The lead molecule, RN-9893 26, inhibited human, rat and murine variants of TRPV4, and showed excellent selectivity over related TRP receptors, such as TRPV1, TRPV3 and TRPM8. The overall profile for RN-9893 may permit its use as a proof-of-concept probe for in vivo applications.