title: Structure-based drug design for dopamine D3 receptor.
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.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu, Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Feng
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
authors.forename: Youyong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006220:Haloperidol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013134:Spiperone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013469:Sulpiride / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C118215:3-(4-(4-chlorophenyl)piperazinylmethyl)pyrazolo(1,5-a)pyridine; C023422:7-azaindole dimer; C467223:FAUC 365; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D050637:Receptors, Dopamine D3; D013876:Thiophenes; D013134:Spiperone; D013469:Sulpiride; D006220:Haloperidol