Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382: A potent and selective positive allosteric modulator of MrgX1

Wandong Wen, Yan Wang, Zhe Li, Pang Yen Tseng, Owen B. McManus, Meng Wu, Min Li, Craig W. Lindsley, Xinzhong Dong, Corey R. Hopkins

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Previous studies have shown that the activation of mouse MrgC11, a G-protein-coupled receptor, by its peptide ligand BAM8-22 can inhibit chronic pain. A large-scale screen has been carried out to isolate small-molecule allosteric agonists of MrgX1, the human homologue of MrgC11. The goal of this study is to improve the efficacy and potency of positive allosteric modulators (PAMs) with therapeutic implications in combating chronic pain. Herein we report an iterative parallel synthesis effort and a structure-activity relationship study of a series of arylsulfonamides which led to the discovery of the first PAM of MrgX1, ML382.

Original languageEnglish (US)
Pages (from-to)57-61
Number of pages5
JournalChemMedChem
Volume10
Issue number1
DOIs
StatePublished - Jan 2015

Keywords

  • Chronic pain
  • ML382
  • MLPCN
  • Molecular probes
  • MrgX1
  • Positive allosteric modulators

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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