ArticleJournal of experimental & clinical cancer research : CR2018
Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Birinapant enhances cisplatin sensitivity in epithelial ovarian cancer through modulation of apoptotic and survival signaling pathways.Cancer chemotherapy and pharmacology · 2026Article
- Context-dependent roles of HtrA2/Omi in ovarian cancer: mitochondrial apoptotic function linking platinum sensitivity and acquired chemoresistance-a narrative review.Translational cancer research · 2026Review
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- Chimeric antigen receptor cells as a tool for localized delivery of TNFα in solid cancer treatment.Human vaccines & immunotherapeutics · 2025Review
- A phase 1 trial of APG-1387, an IAP antagonist, with nab-paclitaxel and gemcitabine in patients with refractory metastatic pancreatic cancer.Cell reports. Medicine · 2025Article
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Chimeric antigen receptor dendritic cells targeted delivery of a single tumoricidal factor for cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2024Article
- Synergistic effects of Smac mimetic APG-1387 with anti-PD-1 antibody are attributed to increased CD3 + NK1.1 + cell recruitment secondary to induction of cytokines from tumor cells.Cancer cell international · 2024Article
- Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins.Journal of medicinal chemistry · 2023Article
- Inhibiting the inhibitors: Development of the IAP inhibitor xevinapant for the treatment of locally advanced squamous cell carcinoma of the head and neck.Cancer treatment reviews · 2023Review
- SMAC Mimetic BV6 Co-Treatment Downregulates the Factors Involved in Resistance and Relapse of Cancer: IAPs and Autophagy.Biology · 2022Article
- Functional Genomic Identification of Predictors of Sensitivity and Mechanisms of Resistance to Multivalent Second-Generation TRAIL-R2 Agonists.Molecular cancer therapeutics · 2022Article
- Establishment and Verification of Logistic Regression Model for Qualitative Diagnosis of Ovarian Cancer Based on MRI and Ultrasound Signs.Computational and mathematical methods in medicine · 2022Article
- Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.ACS pharmacology & translational science · 2021Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Critical roles of Rad54 in tolerance to apigenin-induced Top1-mediated DNA damage.Experimental and therapeutic medicine · 2021Article
- Potential Molecular Mechanism of TNF Superfamily-Related Genes in Glioblastoma Multiforme Based on Transcriptome and Epigenome.Frontiers in neurology · 2021Article
- Review
- Future Therapeutic Directions for Smac-Mimetics.Cells · 2020Review
- Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE.Journal of biomedical science · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOvarian cancer is a deadly disease. Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. Overexpression of IAPs proteins has been correlated with tumorigenesis, treatment resistance and poor prognosis. Reinstalling functional cell death machinery by pharmacological inhibition of IAPs proteins may represent an attractive therapeutic strategy for treatment of ovarian cancer.
methodsCCK-8 and colony formation assay was performed to examine cytotoxic activity. Apoptosis was analyzed by fluorescence microscopy, flow cytometry and TUNEL assay. Elisa assay was used to determine TNFα protein. Caspase activity assay was used for caspase activation evaluation. Immunoprecipitation and siRNA interference were carried out for functional analysis. Western blotting analysis were carried out to test protein expression. Ovarian cancer cell xenograft nude mice model was used for in vivo efficacy evaluation.
resultsAPG-1387 demonstrated potent inhibitory effect on ovarian cancer cell growth and clonogenic cell survival. APG-1387 induced RIP1- and TNFα-dependent apoptotic cell death in ovarian cancer through downregulation of IAPs proteins and induction of caspase-8/FADD/RIP1 complex, which drives caspase-8 activation. NF-κB signaling pathway was activated upon APG-1387 treatment and RIP1 contributed to NF-κB activation. APG-1387 induced cytoprotective autophagy while triggering apoptosis in ovarian cancer cells and inhibition of autophagy enhanced APG-1387-induced apoptotic cell death. APG-1387 exhibited potent antitumor activity against established human ovarian cancer xenografts.
conclusionsOur results demonstrate that APG-1387 targets IAPs proteins to potently elicit apoptotic cell death in vitro and in vivo, and provide mechanistic and applicable rationale for future clinical evaluation of APG-1387 in ovarian cancer.
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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.