ArticleProteins2015
Homology models of the HIV-1 attachment inhibitor BMS-626529 bound to gp120 suggest a unique mechanism of action.
Article in Proteins, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Exploring the impact of baseline and on-treatment variables on durability of responses to fostemsavir through weeks 96 and 192 in the phase 3 BRIGHTE study.HIV medicine · 2026Trial
- Patient-Reported Outcomes in the Phase III BRIGHTE Trial of the HIV-1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Individuals.The patient · 2022Trial
- Effects of Temsavir, Active Moiety of Antiretroviral Agent Fostemsavir, on QT Interval: Results From a Phase I Study and an Exposure-Response Analysis.Clinical and translational science · 2020Trial
- Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir.Journal of acquired immune deficiency syndromes (1999) · 2018Trial
- Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529.Antimicrobial agents and chemotherapy · 2016Trial
- Pharmacokinetic interactions between BMS-626529, the active moiety of the HIV-1 attachment inhibitor prodrug BMS-663068, and ritonavir or ritonavir-boosted atazanavir in healthy subjects.Antimicrobial agents and chemotherapy · 2015Trial
- Comprehensive mapping of the virus and host factors that guide the paths of HIV-1 escape from a therapeutic.Cell reports · 2026Article
- HIV-1 Env Heterogeneity: Cleavage, Trafficking, and Antigenic Consequences for Virions and Infected Cells.Viruses · 2026Review
- Comprehensive Mapping of the Virus and Host Factors that Guide the Paths of HIV-1 Escape from a Therapeutic.bioRxiv : the preprint server for biology · 2025Article
- Population pharmacokinetics and exposure-response relationship for temsavir following fostemsavir administration in treatment-experienced HIV patients.Pharmacology research & perspectives · 2025Article
- High HIV-1 viremia and low anti-Env antibody responses are associated with delayed treatment response to fostemsavir in highly treatment-experienced individuals.Antiviral research · 2025Article
- A Narrative Review of Novel Agents for Managing Heavily Treatment-Experienced People Living With HIV.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2024Review
- Mechanism of action, resistance, interaction, pharmacokinetics, pharmacodynamics, and safety of fostemsavir.BMC infectious diseases · 2024Review
- Antiviral Agents: Structural Basis of Action and Rational Design.Sub-cellular biochemistry · 2024Review
- Structure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir.Nature communications · 2023Article
- Article
- New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?FEMS microbiology reviews · 2023Review
- Enhancement of CD4 Binding, Host Cell Entry, and Sensitivity to CD4bs Antibody Inhibition Conferred by a Natural but Rare Polymorphism in the HIV-1 Envelope.Journal of virology · 2022Article
- Review
- Pharmacokinetics of Temsavir, the Active Moiety of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir, Coadministered with Cobicistat, Etravirine, Darunavir/Cobicistat, or Darunavir/Ritonavir with or without Etravirine in Healthy Participants.Antimicrobial agents and chemotherapy · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 gp120 undergoes multiple conformational changes both before and after binding to the host CD4 receptor. BMS-626529 is an attachment inhibitor (AI) in clinical development (administered as prodrug BMS-663068) that binds to HIV-1 gp120. To investigate the mechanism of action of this new class of antiretroviral compounds, we constructed homology models of unliganded HIV-1 gp120 (UNLIG), a pre-CD4 binding-intermediate conformation (pCD4), a CD4 bound-intermediate conformation (bCD4), and a CD4/co-receptor-bound gp120 (LIG) from a series of partial structures. We also describe a simple pathway illustrating the transition between these four states. Guided by the positions of BMS-626529 resistance substitutions and structure-activity relationship data for the AI series, putative binding sites for BMS-626529 were identified, supported by biochemical and biophysical data. BMS-626529 was docked into the UNLIG model and molecular dynamics simulations were used to demonstrate the thermodynamic stability of the different gp120 UNLIG/BMS-626529 models. We propose that BMS-626529 binds to the UNLIG conformation of gp120 within the structurally conserved outer domain, under the antiparallel β20-β21 sheet, and adjacent to the CD4 binding loop. Through this binding mode, BMS-626529 can inhibit both CD4-induced and CD4-independent formation of the "open state" four-stranded gp120 bridging sheet, and the subsequent formation and exposure of the chemokine co-receptor binding site. This unique mechanism of action prevents the initial interaction of HIV-1 with the host CD4+ T cell, and subsequent HIV-1 binding and entry. Our findings clarify the novel mechanism of BMS-626529, supporting its ongoing clinical development.
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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.