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  • Title: Knowledge-based analysis of multi-potent G-protein coupled receptors ligands.
    Author: Faure P, Dubus E, Ijjaali I, Morlière C, Barberan O, Petitet F.
    Journal: Eur J Med Chem; 2010 Dec; 45(12):5708-17. PubMed ID: 20933307.
    Abstract:
    A large number of chemical structures that interact with G-protein coupled receptors (GPCRs) have been disclosed in patents or published papers. Most of these compounds are selective for a given protein target; however, it is well recognized that some GPCR-drugs interact with multiple targets. Using a literature database, we have identified compounds that act on different GPCRs. These protein targets are usually divided in three main classes, A, B and C, based on sequence similarity, but they can also be grouped pharmacologically based on endogenous ligand characteristics. In this paper, we specifically focus on compounds able to recognize two different classes or different pharmacological clusters within the same class. Despite the large number of GPCR ligands described in the literature, we identified a limited number of molecules acting on both classes A and B, only few acting on classes A and C and none acting on class B and C receptors. A search for bi- or multi-potent compounds exhibiting activities on different pharmacological clusters of class A receptors revealed cases of cross reactivity, the most frequent concerning amine and peptide receptor clusters.
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