ArticleCell stem cell2019
MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo.
Article in Cell stem cell, 2019. 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 55 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
55 citing papers in PubMed, 106 citations in OpenAlex.
- Phosphatidylserine-based liposomes encapsulating DMX-5804 protect against doxorubicin-induced cardiotoxicity.RSC pharmaceutics · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- MAP4K4 inhibition enhances the anti-ferroptosis effect of the FTO/YAP/ATF4 axis in doxorubicin-induced cardiotoxicity.Cell biology and toxicology · 2026Article
- Review
- A human iPSC-derived sensory neuron platform for high-throughput discovery of neuroprotectants against chemotherapy-induced peripheral neuropathy.Cell reports. Medicine · 2026Article
- Phosphatidylserine-Based Liposomes Encapsulating DMX-5804 Protect Against Doxorubicin-Induced Cardiotoxicity.bioRxiv : the preprint server for biology · 2026Article
- A Refined Approach to Permanent Coronary Artery Ligation in Rats: Enhancing Outcomes and Reducing Animal Burden.Animals : an open access journal from MDPI · 2025Article
- Cardioprotective Effects of Simvastatin in Doxorubicin-Induced Acute Cardiomyocyte Injury.International journal of molecular sciences · 2025Article
- Cardiac Tissue Engineering for Translational Cardiology: From In Vitro Models to Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- TNIK: A redox sensor in endothelial cell permeability.Science advances · 2024Article
- GCKIII kinases control hepatocellular lipid homeostasis via shared mode of action.Journal of lipid research · 2024Article
- Striatin plays a major role in angiotensin II-induced cardiomyocyte and cardiac hypertrophy in mice in vivo.Clinical science (London, England : 1979) · 2024Article
- MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.Cardiovascular diabetology · 2024Article
- MAP4Ks inhibition promotes retinal neuron regeneration from Müller glia in adult mice.NPJ Regenerative medicine · 2023Article
- MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.Oncogene · 2023Article
- FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer.Communications biology · 2023Article
- Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC Working Group on Myocardial Function and the ESC Working Group on Cellular Biology of the Heart.Cardiovascular research · 2022Article
- LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistentVirulence · 2022Article
- Article
- Repurposing drugs to treat cardiovascular disease in the era of precision medicine.Nature reviews. Cardiology · 2022Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
34 authors at 5 institutions in 3 countries.
Funding
Abstract
Heart disease is a paramount cause of global death and disability. Although cardiomyocyte death plays a causal role and its suppression would be logical, no clinical counter-measures target the responsible intracellular pathways. Therapeutic progress has been hampered by lack of preclinical human validation. Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) is activated in failing human hearts and relevant rodent models. Using human induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) and MAP4K4 gene silencing, we demonstrate that death induced by oxidative stress requires MAP4K4. Consequently, we devised a small-molecule inhibitor, DMX-5804, that rescues cell survival, mitochondrial function, and calcium cycling in hiPSC-CMs. As proof of principle that drug discovery in hiPSC-CMs may predict efficacy in vivo, DMX-5804 reduces ischemia-reperfusion injury in mice by more than 50%. We implicate MAP4K4 as a well-posed target toward suppressing human cardiac cell death and highlight the utility of hiPSC-CMs in drug discovery to enhance cardiomyocyte survival.
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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.