Forskning ved Københavns Universitet - Københavns Universitet


Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Thomas M Bridges
  • Joy E Marlo
  • Colleen M Niswender
  • Carrie K Jones
  • Satyawan B Jadhav
  • Patrick R Gentry
  • Hyekyung C Plumley
  • C David Weaver
  • P Jeffrey Conn
  • Craig W Lindsley

This report describes the discovery and initial characterization of the first positive allosteric modulator of muscarinic acetylcholine receptor subtype 5 (mAChR5 or M5). Functional HTS, identified VU0119498, which displayed micromolar potencies for potentiation of acetylcholine at M1, M3, and M5 receptors in cell-based Ca(2+) mobilization assays. Subsequent optimization led to the discovery of VU0238429, which possessed an EC(50) of approximately 1.16 microM at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity.

TidsskriftJournal of Medicinal Chemistry
Udgave nummer11
Sider (fra-til)3445-8
Antal sider4
StatusUdgivet - 11 jun. 2009
Eksternt udgivetJa

ID: 213627227