ArticleOncotarget2015
A novel small-molecule IAP antagonist, AZD5582, draws Mcl-1 down-regulation for induction of apoptosis through targeting of cIAP1 and XIAP in human pancreatic cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- UbiDash: A UPS proteomic atlas for tissue-aware degrader design.Cell death and differentiation · 2026Article
- IAP Antagonists Selectively Eliminate Therapy-Induced Senescent Cancer Cells via TNFα-Independent Apoptosis.Cancer science · 2026Article
- Limitations and use of the Morpheus-V5 dual reporter virus in assessing interventions that target HIV latency.Journal of virological methods · 2025Article
- PANoptosis-related gene APAF1 may contribute to the progression of sepsis.Irish journal of medical science · 2025Article
- Integrated single-cell and bulk RNA-sequencing data reveal prognosis and therapeutic response in low-grade glioma based on hypoxia-lactylation related genes.Discover oncology · 2025Article
- Gemcitabine resistance by CITED4 upregulation via the regulation of BIRC2 expression in pancreatic cancer.Journal of biomedical science · 2025Article
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- Therapeutic potential of SHCBP1 inhibitor AZD5582 in pancreatic cancer treatment.Cancer science · 2024Article
- A new era: tumor microenvironment in chemoresistance of pancreatic cancer.Journal of cancer science and clinical therapeutics · 2022Article
- NF-κB and Pancreatic Cancer; Chapter and Verse.Cancers · 2021Review
- Combined inhibition of XIAP and BCL2 drives maximal therapeutic efficacy in genetically diverse aggressive acute myeloid leukemia.Nature cancer · 2021Article
- The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy.Frontiers in immunology · 2021Article
- Chemosensitivity to HM90822, a novel synthetic IAP antagonist, is determined by p-AKT-inducible XIAP phosphorylation in human pancreatic cancer cells.Investigational new drugs · 2020Article
- An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2018Article
- Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells.International journal of molecular sciences · 2018Review
- Baculoviral IAP Repeat Containing 6 (BIRC6) Is a Predictor of Prognosis in Prostate Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.Theranostics · 2018Article
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitor of apoptosis proteins (IAPs) plays an important role in controlling cancer cell survival. IAPs have therefore attracted considerable attention as potential targets in anticancer therapy. In this study, we investigated the anti-tumor effect of AZD5582, a novel small-molecule IAP inhibitor, in human pancreatic cancer cells. Treating human pancreatic cancer cells with AZD5582 differentially induced apoptosis, dependent on the expression of p-Akt and p-XIAP. Moreover, the knockdown of endogenous Akt or XIAP via RNA interference in pancreatic cancer cells, which are resistant to AZD5582, resulted in increased sensitivity to AZD5582, whereas ectopically expressing Akt or XIAP led to resistance to AZD5582. Additionally, AZD5582 targeted cIAP1 to induce TNF-α-induced apoptosis. More importantly, AZD5582 induced a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL. Interestingly, ectopically expressing XIAP and cIAP1 inhibited the AZD5582-induced decrease of Mcl-1 protein, which suggests that AZD5582 elicits Mcl-1 decrease for apoptosis induction by targeting of XIAP and cIAP1. Taken together, these results indicate that sensitivity to AZD5582 is determined by p-Akt-inducible XIAP phosphorylation and by targeting cIAP1. Furthermore, Mcl-1 in pancreatic cancer may act as a potent marker to analyze the therapeutic effects of AZD5582.
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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.