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Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.
Wei, Zhi-Liang; Nguyen, Margaret T; O'Mahony, Donogh J R; Acevedo, Alejandra; Zipfel, Sheila; Zhang, Qingling; Liu, Luna; Dourado, Michelle; Chi, Candace; Yip, Victor; DeFalco, Jeff; Gustafson, Amy; Emerling, Daniel E; Kelly, Michael G; Kincaid, John; Vincent, Fabien; Duncton, Matthew A J.
Afiliação
  • Wei ZL; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Nguyen MT; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • O'Mahony DJ; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Acevedo A; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Zipfel S; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Zhang Q; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Liu L; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Dourado M; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Chi C; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Yip V; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • DeFalco J; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Gustafson A; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Emerling DE; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Kelly MG; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Kincaid J; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States.
  • Vincent F; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States. Electronic address: fabien_vincent_us@yahoo.com.
  • Duncton MA; Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, United States. Electronic address: mattduncton@yahoo.com.
Bioorg Med Chem Lett ; 25(18): 4011-5, 2015 Sep 15.
Article em En | MEDLINE | ID: mdl-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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Canais de Cátion TRPV Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Canais de Cátion TRPV Idioma: En Ano de publicação: 2015 Tipo de documento: Article