Allosteric modulators of G-protein-coupled receptors

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.

Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalCurrent Opinion in Pharmacology
Volume3
Issue number5
DOIs
Publication statusPublished - Oct 2003
Externally publishedYes

Cite this

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Allosteric modulators of G-protein-coupled receptors. / May, Lauren T.; Christopoulos, Arthur.

In: Current Opinion in Pharmacology, Vol. 3, No. 5, 10.2003, p. 551-556.

Research output: Contribution to journalReview ArticleResearchpeer-review

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AU - Christopoulos, Arthur

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AB - Allosteric modulators of G-protein-coupled receptors (GPCRs) interact with binding sites on the receptor that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Allosteric modulators offer several advantages over standard orthosteric drugs, including the potential for greater receptor subtype selectivity. To date, the current paucity of clinically available allosteric drugs reflects the bias of traditional radioligand binding assays towards the detection of orthosteric effects. However, the advent of new cell-based high-throughput functional assays has led to an increased detection of allosteric GPCR ligands. The current challenge for modulator-based GPCR drug discovery is the optimization of both binding and functional assays to better detect and validate allosteric ligands.

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