ArticleToxins2010
The protein kinase C agonist PEP005 (ingenol 3-angelate) in the treatment of human cancer: a balance between efficacy and toxicity.
Article in Toxins, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 62 citations in OpenAlex.
- Atypical protein kinase C activation drives intestinal glucose excretion in diabetes mellitus.Nature communications · 2026Article
- Ingenol mebutate in cancer therapy: mechanisms, clinical applications and future directions.Medical oncology (Northwood, London, England) · 2025Review
- An Ingenane-Type Diterpene fromInternational journal of molecular sciences · 2024Article
- Application and investigation of thrombopoiesis-stimulating agents in the treatment of thrombocytopenia.Therapeutic advances in hematology · 2023Review
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- Analyzing the Systems Biology Effects of COVID-19 mRNA Vaccines to Assess Their Safety and Putative Side Effects.Pathogens (Basel, Switzerland) · 2022Article
- PKC agonism restricts innate immune suppression, promotes antigen cross-presentation and synergizes with agonistic CD40 antibody therapy to activate CD8Cancer letters · 2022Article
- A Comparison of Network-Based Methods for Drug Repurposing along with an Application to Human Complex Diseases.International journal of molecular sciences · 2022Article
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
- Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics.ACS medicinal chemistry letters · 2020Article
- Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives.Cell death discovery · 2020Review
- Semi-Synthetic Ingenol Derivative from Euphorbia tirucalli Inhibits Protein Kinase C Isotypes and Promotes Autophagy and S-phase Arrest on Glioma Cell Lines.Molecules (Basel, Switzerland) · 2019Article
- Mechanism of inhibition of Shiga-toxigenicCell death discovery · 2018Article
- Updates on Psoriasis and Cutaneous Oncology: Proceedings from the 2017 MauiDerm Meeting.The Journal of clinical and aesthetic dermatology · 2017Article
- Ingenol Disoxate: A Novel 4-Isoxazolecarboxylate Ester of Ingenol with Improved Properties for Treatment of Actinic Keratosis and Other Non-Melanoma Skin Cancers.Dermatology and therapy · 2016Article
- Digging deep into "dirty" drugs - modulation of the methylation machinery.Drug metabolism reviews · 2015Review
- Ingenol mebutate: a succinct review of a succinct therapy.Dermatology and therapy · 2014Article
- Novel medical strategies combating nonmelanoma skin cancer.Indian journal of dermatology · 2014Review
- Article
- Recurrent in situ melanoma successfully treated with ingenol mebutate.Dermatology and therapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The diterpene ester ingenol-3-angelate (referred to as PEP005) is derived from the plant Euphorbia peplus. Crude euphorbia extract causes local toxicity and transient inflammation when applied topically and has been used in the treatment of warts, skin keratoses and skin cancer. PEP005 is a broad range activator of the classical (α, β, γ) and novel (δ, ε, η, θ) protein kinase C isoenzymes. Direct pro-apoptotic effects of this drug have been demonstrated in several malignant cells, including melanoma cell lines and primary human acute myelogenous leukemia cells. At micromolar concentrations required to kill melanoma cells this agent causes PKC-independent secondary necrosis. In contrast, the killing of leukemic cells occurs in the nanomolar range, requires activation of protein kinase C δ (PKCδ) and is specifically associated with translocation of PKCδ from the cytoplasm to the nuclear membrane. However, in addition to this pro-apoptotic effect the agent seems to have immunostimulatory effects, including: (i) increased chemokine release by malignant cells; (ii) a general increase in proliferation and cytokine release by activated T cells, including T cells derived from patients with chemotherapy-induced lymphopenia; (iii) local infiltration of neutrophils after topical application with increased antibody-dependent cytotoxicity; and (iv) development of specific anti-cancer immune responses by CD8(+) T cells in animal models. Published studies mainly describe effects from in vitro investigations or after topical application of the agent, and careful evaluation of the toxicity after systemic administration is required before the possible use of this agent in the treatment of malignancies other than skin cancers.
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What OpenQuestion holds
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.