Allosteric Modulation of Class A GPCRs

Targets, Agents, and Emerging Concepts

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

G-protein-coupled receptors (GPCRs) have been tractable drug targets for decades with over one-third of currently marketed drugs targeting GPCRs. Of these, the class A GPCR superfamily is highly represented, and continued drug discovery for this family of receptors may provide novel therapeutics for a vast range of diseases. GPCR allosteric modulation is an innovative targeting approach that broadens the available small molecule toolbox and is proving to be a viable drug discovery strategy, as evidenced by recent FDA approvals and clinical trials. Numerous class A GPCR allosteric modulators have been discovered recently, and emerging trends such as the availability of GPCR crystal structures, diverse functional assays, and structure-based computational approaches are improving optimization and development. This Perspective provides an update on allosterically targeted class A GPCRs and their disease indications and the medicinal chemistry approaches toward novel allosteric modulators and highlights emerging trends and opportunities in the field.

Original languageEnglish (US)
Pages (from-to)88-127
Number of pages40
JournalJournal of Medicinal Chemistry
Volume62
Issue number1
DOIs
StatePublished - Oct 1 2019

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G-Protein-Coupled Receptors
Drug Discovery
Pharmaceutical Chemistry
Drug Delivery Systems
Clinical Trials
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Allosteric Modulation of Class A GPCRs : Targets, Agents, and Emerging Concepts. / Wold, Eric A.; Chen, Jianping; Cunningham, Kathryn; Zhou, Jia.

In: Journal of Medicinal Chemistry, Vol. 62, No. 1, 01.10.2019, p. 88-127.

Research output: Contribution to journalArticle

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