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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.
Pubmed ID: 30853557 RIS Download
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An Antibody supplier
Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain
View all literature mentionsThis polyclonal secondary targets Immunoglobulins
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis monoclonal targets Troponin T-C (1F2)
View all literature mentionsThis monoclonal targets Src
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain MAb (Clone MF20)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets caspase-3
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis polyclonal targets p38 MAPK
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospholamban
View all literature mentionsThis monoclonal targets MAP4K4
View all literature mentionsThis unknown targets Mouse
View all literature mentionsThis polyclonal targets TNNI3
View all literature mentionsThis monoclonal targets Tropomyosin (Sarcomeric)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets alpha-Actinin (Sarcomeric)
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain
View all literature mentionsThis monoclonal targets Troponin T-C (1F2)
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets alpha-Actinin (Sarcomeric)
View all literature mentionsThis polyclonal secondary targets Immunoglobulins
View all literature mentionsThis monoclonal targets Src
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets MAP4K4
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Phospholamban
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain MAb (Clone MF20)
View all literature mentionsThis polyclonal targets TNNI3
View all literature mentionsThis monoclonal targets Tropomyosin (Sarcomeric)
View all literature mentionsThis monoclonal targets Src
View all literature mentionsThis monoclonal targets Troponin T-C (1F2)
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain
View all literature mentionsThis unknown targets Mouse
View all literature mentionsThis polyclonal secondary targets Immunoglobulins
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis monoclonal targets Human Myosin Heavy Chain MAb (Clone MF20)
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis polyclonal targets p38 MAPK
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets caspase-3
View all literature mentionsThis polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
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