title: GPCR homomers and heteromers: a better choice as targets for drug development than GPCR monomers?
abstract: 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.
authors: Departament de Bioquímica i Biologia Molecular, CIBERNED (Centro de Investigación en Red de Enfermedades Neurodegenerativas) and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain.
authors: Vicent
authors: V
authors: Casadó
authors: Antoni
authors: A
authors: Cortés
authors: Josefa
authors: J
authors: Mallol
authors: Kamil
authors: K
authors: Pérez-Capote
authors: Sergi
authors: S
authors: Ferré
authors: Carmen
authors: C
authors: Lluis
authors: Rafael
authors: R
authors: Franco
authors: Enric I
authors: EI
authors: Canela
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000639:trends*; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled