Journal
PHARMACOLOGY & THERAPEUTICS
Volume 124, Issue 2, Pages 248-257Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2009.07.005
Keywords
Equilibrium constants; Binding assays; Cooperativity; G protein-coupled receptors; Receptor heteromers; Receptor dimers
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Funding
- Intramural NIH HHS [Z99 DA999999] Funding Source: Medline
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G protein-coupled receptors (GPCR) are targeted by many therapeutic drugs marketed to fight against a variety of diseases. Selection of novel lead compounds are based on pharmacological parameters obtained assuming that GPCR are monomers. However, many GPCR are expressed as dimers/oligomers. Therefore, drug development may consider GPCR as homo- and hetero-oligomers. A two-state dimer receptor model is now available to understand GPCR operation and to interpret data obtained from drugs interacting with dimers, and even from mixtures of monomers and dimers. Heteromers are distinct entities and therefore a given drug is expected to have different affinities and different efficacies depending on the heteromer. All these concepts would lead to broaden the therapeutic potential of drugs targeting GPCRs, including receptor heteromer-selective drugs with a lower incidence of side effects, or to identify novel pharmacological profiles using cell models expressing receptor heteromers. (C) 2009 Elsevier Inc. All rights reserved.
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