ArticleJournal of medicinal chemistry2014
Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Bisindole Compounds-Synthesis and Medicinal Properties.Antibiotics (Basel, Switzerland) · 2024Review
- Targeting a Conserved Lysine in the Hydrophobic Pocket of HIV-1 gp41 Improves Small Molecule Antiviral Activity.Viruses · 2022Article
- Novel 2-alkylthio-1-benzylimidazole-5-carboxylic Acid Derivatives Targeting Gp41: Design, Synthesis, andCurrent HIV research · 2022Article
- A targeted covalent small molecule inhibitor of HIV-1 fusion.Chemical communications (Cambridge, England) · 2021Article
- Biophysical studies of HIV-1 glycoprotein-41 interactions with peptides and small molecules - Effect of lipids and detergents.Biochimica et biophysica acta. General subjects · 2020Article
- Entry Inhibitors: Efficient Means to Block Viral Infection.The Journal of membrane biology · 2020Review
- A Novel gp41-Binding Adnectin with Potent Anti-HIV Activity Is Highly Synergistic when Linked to a CD4-Binding Adnectin.Journal of virology · 2018Article
- Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41.Organic & biomolecular chemistry · 2017Article
- Enhanced potency of bivalent small molecule gp41 inhibitors.Bioorganic & medicinal chemistry · 2017Article
- Site-specific Isopeptide Bridge Tethering of Chimeric gp41 N-terminal Heptad Repeat Helical Trimers for the Treatment of HIV-1 Infection.Scientific reports · 2016Article
- Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41.Current topics in medicinal chemistry · 2016Review
- Swapped-domain constructs of the glycoprotein-41 ectodomain are potent inhibitors of HIV infection.ACS chemical biology · 2015Article
- Design and characterization of swapped-domain constructs of HIV-1 glycoprotein-41 as receptors for drug discovery.Protein engineering, design & selection : PEDS · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure-activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell-cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biological activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC50 against cell-cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biological activity. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion and demonstrates a potent low molecular weight fusion inhibitor.
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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.