ArticleScience translational medicine2018
Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06258629 (Resident of Clinical Pathology in Sohag Oncology Center), which is not on this map. Cited by 148 papers, 2 of them syntheses that pooled it.
What it found
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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.
Resident of Clinical Pathology in Sohag Oncology Center
Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- The Correlation of Mouse Double Minute 4 (MDM4) Polymorphisms (rs4245739, rs1563828, rs11801299, rs10900598, and rs1380576) with Cancer Susceptibility: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2022Pooled it
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- The Enigmatic Tumor Suppressor p53 Biomolecule: Its Role and Prognostic and Predictive Values in Cancer Therapy and Precision Medicine.Biomolecules · 2026Review
- Transient p53/p21 activation selectively protects healthy human hair follicles and their stem cells from chemotherapy.The Journal of clinical investigation · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Unraveling the role ofHemaSphere · 2026Review
- Synthesis and Biological Evaluation of a Novel Dual-Targeting Small Molecule Drug Conjugate Modulating the Crosstalk between α5β1 Integrin and MDM2 in Glioblastoma.ACS medicinal chemistry letters · 2026Article
- MDM2 in Tumor Biology and Cancer Therapy: A Review of Current Clinical Trials.International journal of molecular sciences · 2025Review
- Regulation of cellular states via targeted phosphorylation of p53 using a nanobody-coupled kinase system.Cell death discovery · 2025Article
- Targeting MDM2 homodimer and heterodimer disruption with DRx-098D inMolecular therapy. Oncology · 2025Article
- Discovery of a Phenylalanine-Derived Natural Compound as a Potential Dual Inhibitor of MDM2 and MDMX.ChemMedChem · 2025Article
- UXT enhances melanoma proliferation, migration, and invasion through modulation of the P53 signaling pathway.Cell division · 2025Article
- The Intrabody Against Murine Double Minute 2 via a p53-Dependent Pathway Induces Apoptosis of Cancer Cell.International journal of molecular sciences · 2025Article
- FLT4 activation promotes acute lymphoid leukemia survival through stabilization of MDM2/MDMX and inactivation of p53.Oncogenesis · 2025Article
- Biomolecular condensation of human IDRs initiates endogenous transcription via intrachromosomal looping or high-density promoter localization.Nucleic acids research · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Searching for novel MDM2/MDMX dual inhibitors through a drug repurposing approach.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- The roles of ubiquitination in AML.Annals of hematology · 2024Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor suppressor p53 is often inactivated via its interaction with endogenous inhibitors mouse double minute 4 homolog (MDM4 or MDMX) or mouse double minute 2 homolog (MDM2), which are frequently overexpressed in patients with acute myeloid leukemia (AML) and other cancers. Pharmacological disruption of both of these interactions has long been sought after as an attractive strategy to fully restore p53-dependent tumor suppressor activity in cancers with wild-type p53. Selective targeting of this pathway has thus far been limited to MDM2-only small-molecule inhibitors, which lack affinity for MDMX. We demonstrate that dual MDMX/MDM2 inhibition with a stapled α-helical peptide (ALRN-6924), which has recently entered phase I clinical testing, produces marked antileukemic effects. ALRN-6924 robustly activates p53-dependent transcription at the single-cell and single-molecule levels and exhibits biochemical and molecular biological on-target activity in leukemia cells in vitro and in vivo. Dual MDMX/MDM2 inhibition by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and apoptosis in cell lines and primary AML patient cells, including leukemic stem cell-enriched populations, and disrupts functional clonogenic and serial replating capacity. Furthermore, ALRN-6924 markedly improves survival in AML xenograft models. Our study provides mechanistic insight to support further testing of ALRN-6924 as a therapeutic approach in AML and other cancers with wild-type p53.
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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.