Literature DB >> 25176330

Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354.

Wandong Wen1, Summer E Young2, Matthew T Duvernay2, Michael L Schulte3, Kellie D Nance3, Bruce J Melancon4, Julie Engers4, Charles W Locuson4, Michael R Wood5, J Scott Daniels4, Wenjun Wu6, Craig W Lindsley5, Heidi E Hamm2, Shaun R Stauffer7.   

Abstract

Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was found to have an IC50 of 140nM for PAR-4 with 71-fold selectivity versus PAR-1 (PAR-1IC50=10μM).
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  ML354; PAR-4 antagonist; Protease activated receptor 4

Mesh：

Substances：

Year:  2014        PMID： 25176330      PMCID： PMC5716344          DOI： 10.1016/j.bmcl.2014.08.021

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


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