Design of bivalent ligands targeting putative GPCR dimers

被引:33
作者
Huang, Boshi [1 ]
St Onge, Celsey M. [1 ]
Ma, Hongguang [1 ]
Zhang, Yan [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Med Chem, Sch Pharm, 800 E Leigh St, Richmond, VA 23298 USA
关键词
MU-OPIOID RECEPTOR; NEUROPATHIC PAIN; AGONIST; DELTA; CHEMOKINE; DIMERIZATION; ANTAGONIST; PHARMACOPHORES; RECOGNITION; COMPLEX;
D O I
10.1016/j.drudis.2020.10.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
G protein-coupled receptors (GPCRs) have been exploited as primary targets for drug discovery, and GPCR dimerization offers opportunities for drug design and disease treatment. An important strategy for targeting putative GPCR dimers is the use of bivalent ligands, which are single molecules that contain two pharmacophores connected through a spacer. Here, we discuss the selection of pharmacophores, the optimal length and chemical composition of the spacer, and the choice of spacer attachment points to the pharmacophores. Furthermore, we review the most recent advances (from 2018 to the present) in the design, discovery and development of bivalent ligands. We aim to reveal the state-of-the-art design strategy for bivalent ligands and provide insights into future opportunities in this promising field of drug discovery.
引用
收藏
页码:189 / 199
页数:11
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