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GPCR homomers and heteromers: A better choice as targets for drug development than GPCR monomers?

2009; Elsevier BV; Volume: 124; Issue: 2 Linguagem: Inglês

10.1016/j.pharmthera.2009.07.005

1879-016X

Vicent Casadó, Antoni Cortés, Josefa Mallol, Kamil Pérez‐Capote, Sergi Ferré, Carmen Lluís, Rafael Franco, Enric I. Canela,

Chemical Synthesis and Analysis

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.