ArticleFrontiers in microbiology2017
A Novel Bromodomain Inhibitor Reverses HIV-1 Latency through Specific Binding with BRD4 to Promote Tat and P-TEFb Association.
Article in Frontiers in microbiology, 2017. 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, 53 citations in OpenAlex.
- Fragment-Based Discovery of BRD4-BD2 Selective Binders: Biophysical Validation and Structural Insights for Domain-Selective Inhibitor Design.ACS omega · 2026Article
- HIV Tat as a latency reversing agent: turning the tables on viral persistence.Frontiers in immunology · 2025Review
- KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.Antiviral research · 2024Article
- Targeting Viral Transcription for HIV Cure Strategies.Microorganisms · 2024Review
- Apabetalone (RVX-208): A Potential Epigenetic Therapy for the Treatment of Cardiovascular, Renal, Neurological, Viral, and Cancer Disorders.ACS pharmacology & translational science · 2024Review
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
- Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.Nature communications · 2023Article
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- Genome-wide CRISPR screens identify combinations of candidate latency reversing agents for targeting the latent HIV-1 reservoir.Science translational medicine · 2022Article
- FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling.Nucleic acids research · 2022Article
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles.Beilstein journal of organic chemistry · 2022Article
- Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration.Frontiers in neuroscience · 2022Review
- Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.Frontiers in microbiology · 2022Review
- A New Small-Molecule Compound, Q308, Silences Latent HIV-1 Provirus by Suppressing Tat- and FACT-Mediated Transcription.Antimicrobial agents and chemotherapy · 2021Article
- Relevance of BET Family Proteins in SARS-CoV-2 Infection.Biomolecules · 2021Review
- In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?Viruses · 2021Review
- Latency Reversing Agents: Kick and Kill of HTLV-1?International journal of molecular sciences · 2021Review
- FACT subunit SUPT16H associates with BRD4 and contributes to silencing of antiviral interferon signaling.bioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency. BETis have emerged as a new class of compounds that are promising for this HIV-1 "shock and kill" eradication approach. However, when used as a single drug, JQ1 only modestly reverses HIV-1 latency, which complicates studying the underlining mechanisms. Meanwhile, it has been widely discussed that the induction of latent proviruses is stochastic (Ho et al., 2013). Thus, new BETis are currently under active development with focus on improving potency, ease of synthesis and structural diversity. Using fluorous-tagged multicomponent reactions, we developed a novel second-generation, 3,5-dimethylisoxazole BETi based on an imidazo[1,2-a] pyrazine scaffold, UMB-32. Furthermore, we screened 37 UMB-32 derivatives and identified that one, UMB-136, reactivates HIV-1 in multiple cell models of HIV-1 latency with better efficiency than either JQ1 or UMB-32. UMB-136 enhances HIV-1 transcription and increases viral production through the release of P-TEFb. Importantly, UMB-136 enhances the latency-reversing effects of PKC agonists (prostratin, bryostatin-1) in CD8-depleted PBMCs containing latent viral reservoirs. Our results illustrate that structurally improved BETis, such as UMB-136, may be useful as promising LRAs for HIV-1 eradication.
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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.