Evidence map›Paper›PMID 39854456›Full record

ArticleScience advances2025

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Zachary O Gentry, Owen D McAteer, Jennifer L Hamad, Jose A Moran, Jocelyn T Kim, Matthew D Marsden, Jerome A Zack, Paul A Wender

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Zachary O GentryDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-0418-6063
Owen D McAteerDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-8576-6253
Jennifer L HamadDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-0806-6835
Jose A MoranDepartment of Microbiology & Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.ORCID 0000-0002-7537-6307
Jocelyn T KimDepartment of Medicine, Division of Infectious Diseases, University of California Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-7040-5773
Matthew D MarsdenDepartment of Microbiology & Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.ORCID 0000-0002-4857-8712
Jerome A ZackDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-5486-8495
Paul A WenderDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-6319-2829

Funding

UCLA-CDU CFARP30AI152501 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Warren Scott Comulada, LaShonda Spencer · 2022 to 2026
$15.6M
SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENTR01CA031845 · NCI · STANFORD UNIVERSITY · PI PAUL Anthony WENDER · 1985 to 2026
$6.9M
Synthetic Studies Related to Cancer Research/TreatmentR37CA031845 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL ANTHONY · 2006 to 2015
$4.5M
Induction of autophagy to enhance CAR-T cells in HIV cure approachesR01AI172727 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARSDEN, MATTHEW DAVID, ZHEN, ANJIE · 2022 to 2025
$3.9M
HIV latency reversal through novel, potent PKC modulatorsR01AI124743 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WENDER, PAUL ANTHONY, ZACK, JEROME A. · 2016 to 2020
$3.3M
Virus-host interactions: a multi-scale training programT32AI007319 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI SEMLER, BERT L, SHI, YONGSHENG · 1988 to 2024
$2.4M
The Effect of Natural Killer Cell-Based Therapy on the HIV ReservoirK08AI155232 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KIM, JOCELYN T · 2020 to 2024
$1.0M
HIV Latency Reversal Through Novel, Potent PKC ModulatorsR56AI124743 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WENDER, PAUL ANTHONY, ZACK, JEROME A. · 2021 to 2021
$798k
NCI NIH HHS R01 CA031845NCI NIH HHS R37 CA031845NIAID NIH HHS K08 AI155232NIAID NIH HHS P30 AI152501NIAID NIH HHS R01 AI124743NIAID NIH HHS R01 AI172727NIAID NIH HHS R56 AI124743NIAID NIH HHS T32 AI007319
6 · The paper itself

Abstract

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported. Enabled by our previously reported scalable synthesis of EBC-46, we report herein the systematic design, synthesis, and evaluation of EBC-46 analogs, including those inaccessible from the natural source and their PKC affinities, ability to translocate PKC, nuclear factor κB activity, and efficacy in reversing HIV latency in Jurkat-Latency cells. Leading analogs show exceptional PKC affinities, isoform selectivities, and functional activities, serving as promising candidates for therapeutic applications.

Indexed as

Anti-HIV AgentsHIV-1HIV InfectionsVirus LatencyHumansJurkat CellsNF-kappa BProtein Kinase CAnti-HIV AgentsNF-kappa BProtein Kinase C

Identifiers

PMID39854456
PMCPMC11778240

What OpenQuestion holds

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Registered trials

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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.