Title:Structure-Based Drug Design for Dopamine D3 Receptor
VOLUME: 15 ISSUE: 10
Author(s):Zhiwei Feng, Tingjun Hou and Youyong Li
Affiliation:Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu, Key Laboratory for Carbon- Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China
Keywords:Crystal structure, D3-receptor, dock, dopamine, drug design, molecular dynamics, SAR.
Abstract:D2-like receptors are members of dopamine receptors, including dopamine D2 receptor (D2R), dopamine D3
receptor (D3R), and dopamine D4 receptor (D4R), which modulate behavior, cognition, and emotion. D2-like receptors
are critical targets for drug development. Particularly, D3R has been identified as a therapeutic target for antipsychotic
and anti-parkinsonian drugs. Recently, the crystal structure of D3R was reported. Here we summarize the available active
compounds for D3R and the structure-activity relationships (SAR) studies of them. This provides lead templates for
further chemical modification. We describe the structure features of the recent crystal structure of D3R and its difference
from other G protein-coupled receptors (GPCRs). We provide the recognition mechanism of the inhibitors of D3R
(molecular docking results and molecular dynamics results), which illustrates the interaction between the inhibitors and
critical residues of D3R. Finally, we summarize the outlook of drug development for D3R. Our study provides useful
information for developing high selective, high potent antagonists and agonists of D3R.
