{"id":6328,"date":"2023-02-17T06:57:10","date_gmt":"2023-02-17T06:57:10","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-map4k4-inhibition-promotes-survival-of-human-stem-cell-derived-cardiomyocytes-and-reduces-infarct-size-in-vivo\/"},"modified":"2023-02-17T06:57:11","modified_gmt":"2023-02-17T06:57:11","slug":"2019-map4k4-inhibition-promotes-survival-of-human-stem-cell-derived-cardiomyocytes-and-reduces-infarct-size-in-vivo","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2019-map4k4-inhibition-promotes-survival-of-human-stem-cell-derived-cardiomyocytes-and-reduces-infarct-size-in-vivo\/","title":{"rendered":"2019 &#8211; MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo"},"content":{"rendered":"<p>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.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,76,77],"therapeutic_areas":[54],"target_categories":[61],"target_families":[332,333],"targets":[92,93],"resource_keyword":[],"class_list":["post-6328","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-nav-channels","target_families-kv-channels","targets-kv11-1-herg","targets-nav1-5"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6328","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6328"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6328"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6328"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6328"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6328"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6328"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6328"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6328"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6328"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}