Abstract
Family C of G-protein coupled receptors (GPCRs) from humans is constituted by eight metabotropic glutamate (mGlu1-8) receptors, two heterodimeric -aminobutyric acidB (GABAB) receptors, a calcium-sensing receptor (CaR), three taste (T1R) receptors, a promiscuous L- α-amino acid receptor (GPRC6A), and five orphan receptors. Aside from the orphan receptors, the family C GPCRs are characterised by a large amino-terminal domain, which bind the endogenous orthosteric agonists. Recently, a number of allosteric modulators binding to the seven transmembrane domains of the receptors have also been reported. Family C GPCRs regulate a number of important physiological functions and are thus intensively pursued as drug targets. So far, two drugs acting at family C receptors (the GABAB agonist baclofen and the positive allosteric CaR modulator cinacalcet) have been marketed. Cinacalcet is the first allosteric GPCR modulator to enter the market, which demonstrates that the therapeutic principle of allosteric modulation can also be extended to this important drug target class. In this review we outline the structure and function of family C GPCRs with particular focus on the ligand binding sites, and we present the most important pharmacological agents and the therapeutic prospects of the receptors.
Keywords: Metabotropic glutamate receptor, calcium-sensing receptor, γ-aminobutyric acidB receptor, GPRC6A
Current Drug Targets
Title: Structure, Pharmacology and Therapeutic Prospects of Family C G-Protein Coupled Receptors
Volume: 8 Issue: 1
Author(s): Hans Brauner-Osborne, Petrine Wellendorph and Anders A. Jensen
Affiliation:
Keywords: Metabotropic glutamate receptor, calcium-sensing receptor, γ-aminobutyric acidB receptor, GPRC6A
Abstract: Family C of G-protein coupled receptors (GPCRs) from humans is constituted by eight metabotropic glutamate (mGlu1-8) receptors, two heterodimeric -aminobutyric acidB (GABAB) receptors, a calcium-sensing receptor (CaR), three taste (T1R) receptors, a promiscuous L- α-amino acid receptor (GPRC6A), and five orphan receptors. Aside from the orphan receptors, the family C GPCRs are characterised by a large amino-terminal domain, which bind the endogenous orthosteric agonists. Recently, a number of allosteric modulators binding to the seven transmembrane domains of the receptors have also been reported. Family C GPCRs regulate a number of important physiological functions and are thus intensively pursued as drug targets. So far, two drugs acting at family C receptors (the GABAB agonist baclofen and the positive allosteric CaR modulator cinacalcet) have been marketed. Cinacalcet is the first allosteric GPCR modulator to enter the market, which demonstrates that the therapeutic principle of allosteric modulation can also be extended to this important drug target class. In this review we outline the structure and function of family C GPCRs with particular focus on the ligand binding sites, and we present the most important pharmacological agents and the therapeutic prospects of the receptors.
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Cite this article as:
Brauner-Osborne Hans, Wellendorph Petrine and Jensen A. Anders, Structure, Pharmacology and Therapeutic Prospects of Family C G-Protein Coupled Receptors, Current Drug Targets 2007; 8 (1) . https://dx.doi.org/10.2174/138945007779315614
DOI https://dx.doi.org/10.2174/138945007779315614 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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