ArticleJournal of medicinal chemistry2020
2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- The structure of the dopamine DScience advances · 2026Article
- Developing the Dopamine D3 Receptor (D3R) Antagonist, (R)-VK4-116, as a Non-Opioid Medication for the Treatment of Opioid Use Disorder.Medicinal research reviews · 2026Review
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- A Ligand-Triggered Receptor Conformation Enables the Design of Selective Agonists for the Dopamine 3 Receptor (DJACS Au · 2026Article
- Structural basis for positive allosteric regulation of CB2 receptor.Nature communications · 2026Article
- Tailoring cariprazine for dual disorders via secondary pharmacophore optimization.European journal of medicinal chemistry · 2026Article
- Development of bitopic nanobody-ligand conjugates targeting G protein-coupled receptors and exhibiting logic-gated signaling.PLoS biology · 2025Article
- Revealing the location and dynamics of a concealed binding site in the dopamine transporter.Nature communications · 2025Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Nanobody-based conjugates targeting small molecule-binding GPCRs and exhibiting logic-gated signaling.bioRxiv : the preprint server for biology · 2025Article
- A bitopic agonist bound to the dopamine 3 receptor reveals a selectivity site.Nature communications · 2024Article
- Linkers in Bitopic Agonists Shape Bias Profile among Transducers for the Dopamine D2 and D3 Receptors.ACS pharmacology & translational science · 2024Article
- Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 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
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Carbazole and tetrahydro-carboline derivatives as dopamine DActa pharmaceutica Sinica. B · 2023Article
- Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine DJournal of medicinal chemistry · 2023Article
- Dopamine DJournal of medicinal chemistry · 2023Article
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Abstract
The genesis of designing bivalent or bitopic molecules that engender unique pharmacological properties began with Portoghese's work directed toward opioid receptors, in the early 1980s. This strategy has evolved as an attractive way to engineer highly selective compounds for targeted G-protein coupled receptors (GPCRs) with optimized efficacies and/or signaling bias. The emergence of X-ray crystal structures of many GPCRs and the identification of both orthosteric and allosteric binding sites have provided further guidance to ligand drug design that includes a primary pharmacophore (PP), a secondary pharmacophore (SP), and a linker between them. It is critical to note the synergistic relationship among all three of these components as they contribute to the overall interaction of these molecules with their receptor proteins and that strategically designed combinations have and will continue to provide the GPCR molecular tools of the future.
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