G-protein-coupled receptor accessory proteins: their potential role in future drug discovery.
Historically, the activation and inhibition of GPCR (G-protein-coupled receptor) function have been a very successful avenue for drug discovery and development. However, it is clear that receptors do not function in isolation but are impacted by other proteins. These proteins may alter either binding or functional responses. Identification and study of these interactions have grown rapidly in recent years and continue to do so, resulting in a plethora of potential receptor-protein connections. These associations can be regarded as alternative intervention points to modulate GPCR function and may not only provide alternative ways to modify receptor activity but also to exploit new chemical space for drug-like molecules. Such interactions may account for side-effects or undesirable properties associated with otherwise well-validated GPCR targets. Understanding and/or intervening in these interactions may allow scientists to progress those targets that may have been deemed unsuitable for therapeutic intervention. The present study reviews the opportunities for utilizing receptor interacting proteins as potential drug targets and the issues associated with them.
Presland
J
J
Molecular Pharmacology, Organon Laboratories Ltd, Newhouse ML1 5SH, Scotland, UK. j.presland@organon.co.uk
D000818:Animals; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000737:chemistry; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins