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Identification of Orally-Bioavailable Antagonists of the TRPV4 Ion-Channel

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, etc.

Bioorg Med Chem Lett. 2015 Sep 15;25(18):4011-5.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1803003680 RN-9893 RN-9893 1803003-68-0 Price
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