Novel inhibitors of MAP4K4 (HGK), an acute therapy to prevent cardiac muscle cell death following myocardial infarction (360G-Wellcome-106328_Z_14_D)

Heart disease is the most frequent source of death and disability worldwide, most especially as heart attacks (cardiac muscle cell death from obstructed blood flow to the heart). Its severity is due in part to heart muscle's inability to rebuild itself as most other tissues can. One potential strategy, to enhance standard therapies like “clot-busting” drugs and stents, is to suppress cell death directly by protecting the injured, jeopardized muscle cells. Professor Michael Schneider at Imperial College London has identified the enzyme MAP4K4 as a key regulator of cardiac cell death and has devised novel, potent, selective drug-like inhibitors to protect human cardiac muscle grown in the laboratory. This Seeding Drug Discovery Award will enable the innovative use of human cardiac muscle grown from stem cells to pinpoint the molecules responsible for cardiac injury and will take the programme of research the essential steps further, towards the development of MAP4K4 inhibitors as clinically workable compounds.