ArticleChemMedChem2013
Identification of a small-molecule inhibitor of HIV-1 assembly that targets the phosphatidylinositol (4,5)-bisphosphate binding site of the HIV-1 matrix protein.
Article in ChemMedChem, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Discovery of 4-Quinazolinone-Containing Phenylalanine Derivatives as Potent, Resistant-Tolerant HIV Capsid Inhibitors.MedComm · 2026Article
- Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches.Cells · 2025Review
- Review
- A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication.International journal of molecular sciences · 2024Review
- Design, synthesis, and mechanistic study of 2-piperazineone-bearing peptidomimetics as novel HIV capsid modulators.RSC medicinal chemistry · 2023Article
- HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The HIV-1 Matrix Protein p17 Does Cross the Blood-Brain Barrier.Journal of virology · 2022Article
- Design, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors.European journal of medicinal chemistry · 2021Article
- Rapid Optimization of the Metabolic Stability of a Human Immunodeficiency Virus Type-1 Capsid Inhibitor Using a Multistep Computational Workflow.Journal of medicinal chemistry · 2021Article
- Review
- Recent Advances in HIV-1 Gag Inhibitor Design and Development.Molecules (Basel, Switzerland) · 2020Review
- Composition and Orientation of the Core Region of Novel HIV-1 Entry Inhibitors Influences Metabolic Stability.Molecules (Basel, Switzerland) · 2020Article
- Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.European journal of medicinal chemistry · 2020Article
- Field-Based Affinity Optimization of a Novel Azabicyclohexane Scaffold HIV-1 Entry Inhibitor.Molecules (Basel, Switzerland) · 2019Article
- Solution Conformation of Bovine Leukemia Virus Gag Suggests an Elongated Structure.Journal of molecular biology · 2019Article
- Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library.European journal of medicinal chemistry · 2018Article
- Kinetic Characterization of Novel HIV-1 Entry Inhibitors: Discovery of a Relationship between Off-Rate and Potency.Molecules (Basel, Switzerland) · 2018Article
- Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.Journal of drug design and research · 2018Article
- Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17.Scientific reports · 2016Article
- HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors.Current topics in medicinal chemistry · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The development of drug resistance remains a critical problem for current HIV-1 antiviral therapies, creating a need for new inhibitors of HIV-1 replication. We previously reported on a novel anti-HIV-1 compound, N(2)-(phenoxyacetyl)-N-[4-(1-piperidinylcarbonyl)benzyl]glycinamide (14), that binds to the highly conserved phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P(2)) binding pocket of the HIV-1 matrix (MA) protein. In this study, we re-evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV-1 replication assay using primary human peripheral blood mononuclear cells. This study resulted in the identification of three new compounds with antiviral activity; 2-(4-{[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl})-1-piperazinyl)-N-(4-methylphenyl)acetamide (7), 3-(2-ethoxyphenyl)-5-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-1,2,4-oxadiazole (17), and N-[4-ethoxy-3-(1-piperidinylsulfonyl)phenyl]-2-(imidazo[2,1-b][1,3]thiazol-6-yl)acetamide (18), with compound 7 being the most potent of these hits. Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV-1 MA. In accordance with our drug target, compound 7 competes with PI(4,5)P(2) for MA binding and, as a result, diminishes the production of new virus. Mutation of residues within the PI(4,5)P(2) binding site of MA decreased the antiviral effect of compound 7. Additionally, compound 7 displays a broadly neutralizing anti-HIV activity, with IC(50) values of 7.5-15.6 μM for the group M isolates tested. Taken together, these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could, through further optimization, lead to a new class of anti-HIV-1 therapeutics.
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Registered trials
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