ArticleCell death discovery2021
MDM2 inhibitor APG-115 exerts potent antitumor activity and synergizes with standard-of-care agents in preclinical acute myeloid leukemia models.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The trial behind it
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer.Clinical and experimental medicine · 2026Article
- A novel pyrrolidine-chalcone derivative exhibits synergistic anti-cervical cancer activity by dual-targeting MDM2-p53 axis and ferroptosis pathway.Frontiers in pharmacology · 2026Article
- APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells.Anti-cancer drugs · 2025Article
- Article
- Corrigendum to Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2025Article
- TP53-Mutated Acute Myeloid Leukemia: Unanswered Questions.Hematological oncology · 2025Review
- The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Novel small-molecule therapies for myelodysplastic syndromes with IPSS-R ⩾3.5 in patients aged 60 or older: current landscape and challenges.Therapeutic advances in hematology · 2025Review
- SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- A first-in-human phase I study of a novel MDM2/p53 inhibitor alrizomadlin in advanced solid tumors.ESMO open · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- p53 at the crossroads of tumor immunity.Nature cancer · 2024Review
- Targeting Hdm2 and Hdm4 in Anticancer Drug Discovery: Implications for Checkpoint Inhibitor Immunotherapy.Cells · 2024Review
- p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications.Biomedicines · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous clonal disease associated with unmet medical needs. Paralleling the pathology of other cancers, AML tumorigenesis and propagation can be ascribed to dysregulated cellular processes, including apoptosis. This function and others are regulated by tumor suppressor P53, which plays a pivotal role in leukemogenesis. Opposing P53-mediated activities is the mouse double minute 2 homolog (MDM2), which promotes P53 degradation. Because the TP53 mutation rate is low, and MDM2 frequently overexpressed, in patients with leukemia, targeting the MDM2-P53 axis to restore P53 function has emerged as an attractive AML treatment strategy. APG-115 is a potent MDM2 inhibitor under clinical development for patients with solid tumors. In cellular cultures and animal models of AML, we demonstrate that APG-115 exerted substantial antileukemic activity, as either a single agent or when combined with standard-of-care (SOC) hypomethylating agents azacitidine (AZA) and decitabine (DAC), or the DNA-damaging agent cytarabine (Ara-C). By activating the P53/P21 pathway, APG-115 exhibited potent antiproliferative and apoptogenic activities, and induced cell cycle arrest, in TP53 wild-type AML lines. In vivo, APG-115 significantly reduced tumor burden and prolonged survival. Combinations of APG-115 with SOC treatments elicited synergistic antileukemic activity. To explain these effects, we propose that APG-115 and SOC agents augment AML cell killing by complementarily activating the P53/P21 pathway and upregulating DNA damage. These findings and the emerging mechanism of action afford a sound scientific rationale to evaluate APG-115 (with or without SOC therapies) in patients with AML.
Identifiers
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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.