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 Citations (Scopus)

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

Fingerprint

Chronic Pain
Modulators
Structure-Activity Relationship
G-Protein-Coupled Receptors
Chemical activation
Ligands
Peptides
Molecules
benzamide
Therapeutics
bovine adrenal medulla 8-22

Keywords

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

ASJC Scopus subject areas

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

Cite this

Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382 : A potent and selective positive allosteric modulator of MrgX1. / Wen, Wandong; Wang, Yan; Li, Zhe; Tseng, Pang Yen; McManus, Owen B.; Wu, Meng; Li, Min; Lindsley, Craig W.; Dong, Xinzhong; Hopkins, Corey R.

In: ChemMedChem, Vol. 10, No. 1, 01.2015, p. 57-61.

Research output: Contribution to journalArticle

Wen, Wandong ; Wang, Yan ; Li, Zhe ; Tseng, Pang Yen ; McManus, Owen B. ; Wu, Meng ; Li, Min ; Lindsley, Craig W. ; Dong, Xinzhong ; Hopkins, Corey R. / Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382 : A potent and selective positive allosteric modulator of MrgX1. In: ChemMedChem. 2015 ; Vol. 10, No. 1. pp. 57-61.
@article{6c16684c6c6e4cacba543061938ec2ca,
title = "Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382: A potent and selective positive allosteric modulator of MrgX1",
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.",
keywords = "Chronic pain, ML382, MLPCN, Molecular probes, MrgX1, Positive allosteric modulators",
author = "Wandong Wen and Yan Wang and Zhe Li and Tseng, {Pang Yen} and McManus, {Owen B.} and Meng Wu and Min Li and Lindsley, {Craig W.} and Xinzhong Dong and Hopkins, {Corey R.}",
year = "2015",
month = "1",
doi = "10.1002/cmdc.201402277",
language = "English (US)",
volume = "10",
pages = "57--61",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382

T2 - A potent and selective positive allosteric modulator of MrgX1

AU - Wen, Wandong

AU - Wang, Yan

AU - Li, Zhe

AU - Tseng, Pang Yen

AU - McManus, Owen B.

AU - Wu, Meng

AU - Li, Min

AU - Lindsley, Craig W.

AU - Dong, Xinzhong

AU - Hopkins, Corey R.

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

KW - Chronic pain

KW - ML382

KW - MLPCN

KW - Molecular probes

KW - MrgX1

KW - Positive allosteric modulators

UR - http://www.scopus.com/inward/record.url?scp=84919740320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919740320&partnerID=8YFLogxK

U2 - 10.1002/cmdc.201402277

DO - 10.1002/cmdc.201402277

M3 - Article

C2 - 25209672

AN - SCOPUS:84919740320

VL - 10

SP - 57

EP - 61

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 1

ER -