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Cheung M, Bao W, Behm DJ, et al. Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS Med Chem Lett. 2017;8(5):549-554doi: 10.1021/acsmedchemlett.7b00094.
Cheung, M., Bao, W., Behm, D. J., Brooks, C. A., Bury, M. J., Dowdell, S. E., Eidam, H. S., Fox, R. M., Goodman, K. B., Holt, D. A., Lee, D., Roethke, T. J., Willette, R. N., Xu, X., Ye, G., & Thorneloe, K. S. (2017). Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS medicinal chemistry letters, 8(5), 549-554. https://doi.org/10.1021/acsmedchemlett.7b00094
Cheung, Mui, et al. "Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4." ACS medicinal chemistry letters vol. 8,5 (2017): 549-554. doi: https://doi.org/10.1021/acsmedchemlett.7b00094
Cheung M, Bao W, Behm DJ, Brooks CA, Bury MJ, Dowdell SE, Eidam HS, Fox RM, Goodman KB, Holt DA, Lee D, Roethke TJ, Willette RN, Xu X, Ye G, Thorneloe KS. Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS Med Chem Lett. 2017 Mar 20;8(5):549-554. doi: 10.1021/acsmedchemlett.7b00094. eCollection 2017 May 11. PMID: 28523109; PMCID: PMC5430398.
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ACS Med Chem Lett. 2017 Mar 20;8(5):549-554. doi: 10.1021/acsmedchemlett.7b00094. eCollection 2017 May 11.

Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4.

ACS medicinal chemistry letters

Mui Cheung, Weike Bao, David J Behm, Carl A Brooks, Michael J Bury, Sarah E Dowdell, Hilary S Eidam, Ryan M Fox, Krista B Goodman, Dennis A Holt, Dennis Lee, Theresa J Roethke, Robert N Willette, Xiaoping Xu, Guosen Ye, Kevin S Thorneloe

Affiliations

  1. GlaxoSmithKline, Heart Failure Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapeutic Area, King of Prussia, Pennsylvania 19406, United States.

PMID: 28523109 PMCID: PMC5430398 DOI: 10.1021/acsmedchemlett.7b00094

Abstract

Transient Receptor Potential Vanilloid 4 (TRPV4) is a member of the Transient Receptor Potential (TRP) superfamily of cation channels. TRPV4 is expressed in the vascular endothelium in the lung and regulates the integrity of the alveolar septal barrier. Increased pulmonary vascular pressure evokes TRPV4-dependent pulmonary edema, and therefore, inhibition of TRPV4 represents a novel approach for the treatment of pulmonary edema associated with conditions such as congestive heart failure. Herein we report the discovery of an orally active, potent, and selective TRPV4 blocker, 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-

Keywords: GSK2193874; L-type channel inhibition; TRPV4; TRPV4 antagonist; TRPV4 inhibitor; congestive heart failure

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