Kopinathan Anitha, Scammells Peter J, Lane J Robert, Capuano Ben
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Future Med Chem. 2016 Jul;8(11):1349-72. doi: 10.4155/fmc-2016-0010. Epub 2016 Jun 30.
The dopamine D2 receptor (D2R) has been implicated in the symptomology of disorders such as schizophrenia and Parkinson's disease. Multivalent ligands provide useful tools to investigate emerging concepts of G protein-coupled receptor drug action such as allostery, bitopic binding and receptor dimerization. This review focuses on the approaches taken toward the development of multivalent ligands for the D2R recently and highlights the challenges associated with each approach, their utility in probing D2R function and approaches to develop new D2R-targeting drugs. Furthermore, we extend our discussion to the possibility of designing multitarget ligands. The insights gained from such studies may provide the basis for improved therapeutic targeting of the D2R.
多巴胺 D2 受体（D2R）与精神分裂症和帕金森病等疾病的症状学有关。多价配体为研究 G 蛋白偶联受体药物作用的新兴概念提供了有用工具，如变构调节、双位点结合和受体二聚化。本综述重点关注近期开发 D2R 多价配体所采用的方法，并强调每种方法所面临的挑战、它们在探究 D2R 功能方面的效用以及开发新型 D2R 靶向药物的方法。此外，我们将讨论扩展到设计多靶点配体的可能性。此类研究获得的见解可能为改善 D2R 的治疗靶点提供基础。
