ArticleJournal of medicinal chemistry2012
Molecular determinants of selectivity and efficacy at the dopamine D3 receptor.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
87 citing papers in PubMed, 178 citations in OpenAlex.
- Hybrid design reveals a dopamine D3R ligand with promising in vitro ADME properties.Bioorganic chemistry · 2026Article
- The structure of the dopamine DScience advances · 2026Article
- A Ligand-Triggered Receptor Conformation Enables the Design of Selective Agonists for the Dopamine 3 Receptor (DJACS Au · 2026Article
- Structural Basis for D3/D4-Selective Antagonism of Piperazinylalkyl Pyrazole/Isoxazole Analogs.Molecules (Basel, Switzerland) · 2025Article
- Discovery, Characterization, and Optimization of a Novel Positive Allosteric Modulator-Antagonist of the DJournal of medicinal chemistry · 2025Article
- A bitopic agonist bound to the dopamine 3 receptor reveals a selectivity site.Nature communications · 2024Article
- Unraveling Activation-Related Rearrangements and Intrinsic Divergence from Ligand-Specific Conformational Changes of the Dopamine D3 and D2 Receptors.Journal of chemical information and modeling · 2024Review
- Structure of the dopamine D3 receptor bound to a bitopic agonist reveals a new specificity site in an expanded allosteric pocket.Research square · 2023Article
- Synthesis of bitopic ligands based on fallypride and evaluation of their affinity and selectivity towards dopamine DEuropean journal of medicinal chemistry · 2023Article
- Unraveling activation-related rearrangements and intrinsic divergence from ligand-induced conformational changes of the dopamine D3 and D2 receptors.bioRxiv : the preprint server for biology · 2023Article
- Optical Control of Dopamine D2-like Receptors with Cell-Specific Fast-Relaxing Photoswitches.Journal of the American Chemical Society · 2023Article
- A Novel "Activation Switch" Motif Common to All Aminergic Receptors.Journal of chemical information and modeling · 2023Review
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine DJournal of medicinal chemistry · 2023Article
- Structural basis of efficacy-driven ligand selectivity at GPCRs.Nature chemical biology · 2023Article
- Dopamine Receptor Ligand Selectivity-An In Silico/In Vitro Insight.Biomedicines · 2023Article
- Design and Synthesis of Conformationally Flexible Scaffold as Bitopic Ligands for Potent DInternational journal of molecular sciences · 2022Article
- Allosteric Modulators of Dopamine DMolecules (Basel, Switzerland) · 2022Review
- Approach to the specificity and selectivity between D2 and D3 receptors by mutagenesis and binding experiments part I: Expression and characterization of D2 and D3 receptor mutants.Protein science : a publication of the Protein Society · 2022Article
- Allosteric modulation of dopamine DPharmacological reports : PR · 2022Article
- Dopamine D3 receptor ligand suppresses the expression of levodopa-induced dyskinesia in nonhuman primate model of parkinson's disease.Experimental neurology · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
The dopamine D3 receptor (D3R) has been implicated in substance abuse and other neuropsychiatric disorders. The high sequence homology between the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has made the development of D3R-selective compounds challenging. Here, we deconstruct into pharmacophoric elements a series of D3R-selective substituted-4-phenylpiperazine compounds and use computational simulations and binding and activation studies to dissect the structural bases for D3R selectivity and efficacy. We find that selectivity arises from divergent interactions within a second binding pocket (SBP) separate from the OBS, whereas efficacy depends on the binding mode in the OBS. Our findings reveal structural features of the receptor that are critical to selectivity and efficacy that can be used to design highly D3R-selective ligands with targeted efficacies. These findings are generalizable to other GPCRs in which the SBP can be targeted by bitopic or allosteric ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.