ArticleProceedings of the National Academy of Sciences of the United States of America2013
Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 148 citations in OpenAlex.
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
- Targeting NF-κB signaling for HIV latency reversal: Mechanisms, challenges, and therapeutic perspectives.Virus research · 2026Review
- Evolution of a Synthetic Strategy for Complex Diterpenes fromJournal of the American Chemical Society · 2026Article
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Traditional Medicine Extracts ofInternational journal of molecular sciences · 2026Article
- Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.Science advances · 2025Article
- Topological Heterogeneity of Protein Kinase C Modulators in Human T-Cells Resolved with In-Cell Dynamic Nuclear Polarization NMR Spectroscopy.Journal of the American Chemical Society · 2024Article
- Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription.Antimicrobial agents and chemotherapy · 2024Article
- Review
- Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda.Heliyon · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.Pathogens & immunity · 2024Article
- Characteristics and mechanisms of latency-reversing agents in the activation of the human immunodeficiency virus 1 reservoir.Archives of virology · 2023Review
- Tigliane and daphnane diterpenoids from Thymelaeaceae family: chemistry, biological activity, and potential in drug discovery.Journal of natural medicines · 2023Review
- Anti-HIV Tigliane-Type Diterpenoids from the Aerial Parts ofJournal of natural products · 2022Article
- Gene discovery and virus-induced gene silencing reveal branched pathways to major classes of bioactive diterpenoids inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Human Immunodeficiency Virus-1 Latency ReversalFrontiers in microbiology · 2022Article
- Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Phytochemistry and Pharmacological Activities of the Diterpenoids from the GenusMolecules (Basel, Switzerland) · 2021Review
- Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways.PLoS pathogens · 2021Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4(+) T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4(+) T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly, selected members were also tested for HIV induction in resting CD4(+) T cells isolated from infected individuals receiving HAART and were found to exhibit potent induction activity. These more potent agents and by extension related tunable analogs now accessible through the studies described herein should facilitate research and preclinical advancement of this strategy for HIV/AIDS eradication.
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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.