Sexton Patrick M, Poyner David R, Simms John, Christopoulos Arthur, Hay Debbie L
Drug Discovery Biology Laboratory, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Victoria 3800, Australia.
Drug Discov Today. 2009 Apr;14(7-8):413-9. doi: 10.1016/j.drudis.2008.12.009. Epub 2009 Jan 16.
G protein-coupled receptors (GPCRs) are successfully exploited as drug targets. As our understanding of how distinct GPCR subtypes can be generated expands, so do possibilities for therapeutic intervention via these receptors. Receptor activity-modifying proteins (RAMPs) are excellent examples of proteins that enhance diversity in GPCR function. They facilitate the creation of binding pockets, controlling the pharmacology of some GPCRs. Moreover, they have the ability to regulate cell-surface trafficking, internalisation and signalling of GPCRs, creating novel opportunities for drug discovery. RAMPs could be directly targeted by drugs, or advantage could be taken of unique RAMP/GPCR interfaces for generating highly selective ligands.
G蛋白偶联受体(GPCRs)已成功用作药物靶点。随着我们对不同GPCR亚型如何产生的理解不断扩展,通过这些受体进行治疗干预的可能性也在增加。受体活性调节蛋白(RAMPs)是增强GPCR功能多样性的蛋白质的杰出例子。它们有助于形成结合口袋,控制某些GPCR的药理学特性。此外,它们有能力调节GPCR的细胞表面转运、内化和信号传导,为药物发现创造了新机会。RAMPs可以直接作为药物靶点,或者利用独特的RAMP/GPCR界面来生成高选择性配体。