ArticleProceedings of the National Academy of Sciences of the United States of America2020
Prodrugs of PKC modulators show enhanced HIV latency reversal and an expanded therapeutic window.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
- Preparation, Oral SNEDDS Formulation, and In Vivo Evaluation of the HIV-1 Latency-Reversing Agent EK-16A.Molecules (Basel, Switzerland) · 2026Article
- Harziachalasins A-G, polycyclic-fused cytochalasins from the endophytic fungus Trichoderma harzianum MLJ-4 with HIV latency reversal activity.Natural products and bioprospecting · 2026Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Effects of Oxygen Atom Position in Linear Side Chains of Ansellone Analogues on HIV Latency-Reversing Activity.ACS medicinal chemistry letters · 2025Article
- Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.Marine drugs · 2025Review
- Design of 20-deoxyingenol-esters-based PKC agonists and their lysosome biogenesis-enhancing activity.Natural products and bioprospecting · 2025Article
- BRD9 functions as an HIV-1 latency regulatory factor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Activating PKC-ε induces HIV expression with improved tolerability.PLoS pathogens · 2025Article
- Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.Science advances · 2025Article
- Review
- Review
- The landscape of small-molecule prodrugs.Nature reviews. Drug discovery · 2024Review
- TPPB modulates PKC activity to attenuate neuroinflammation and ameliorate experimental multiple sclerosis.bioRxiv : the preprint server for biology · 2024Article
- Quantification of Binding of Small Molecules to Native Proteins Overexpressed in Living Cells.Journal of the American Chemical Society · 2024Article
- ISG15-LFA1 interactions in latent HIV clearance: mechanistic implications in designing antiviral therapies.Frontiers in cell and developmental biology · 2024Article
- TPPB modulates PKC activity to attenuate neuroinflammation and ameliorate experimental multiple sclerosis.Frontiers in cellular neuroscience · 2024Article
- Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.Pathogens & immunity · 2024Article
- Tigliane and daphnane diterpenoids from Thymelaeaceae family: chemistry, biological activity, and potential in drug discovery.Journal of natural medicines · 2023Review
- Automated microarray platform for single-cell sorting and collection of lymphocytes following HIV reactivation.Bioengineering & translational medicine · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
AIDS is a pandemic disease caused by HIV that affects 37 million people worldwide. Current antiretroviral therapy slows disease progression but does not eliminate latently infected cells, which resupply active virus, thus necessitating lifelong treatment with associated compliance, cost, and chemoexposure issues. Latency-reversing agents (LRAs) activate these cells, allowing for their potential clearance, thus presenting a strategy to eradicate the infection. Protein kinase C (PKC) modulators-including prostratin, ingenol esters, bryostatin, and their analogs-are potent LRAs in various stages of development for several clinical indications. While LRAs are promising, a major challenge associated with their clinical use is sustaining therapeutically meaningful levels of the active agent while minimizing side effects. Here we describe a strategy to address this problem based on LRA prodrugs, designed for controllable release of the active LRA after a single injection. As intended, these prodrugs exhibit comparable or superior in vitro activity relative to the parent compounds. Selected compounds induced higher in vivo expression of CD69, an activation biomarker, and, by releasing free agent over time, significantly improved tolerability when compared to the parent LRAs. More generally, selected prodrugs of PKC modulators avoid the bolus toxicities of the parent drug and exhibit greater efficacy and expanded tolerability, thereby addressing a longstanding objective for many clinical applications.
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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.