DMX-5804

Description: DMX-5804 is a novel, potent, orally bioactive and selective MAP4K4 (Mitogen-activated protein kinase kinase kinase kinase-4) inhibitor with an IC50 of 3 nM, a pIC50 of 8.55 for human MAP4K4, less potent on MINK1/MAP4K6 (pIC50, 8.18), and TNIK/MAP4K7 (pIC50, 7.96). DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice. 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.

References: Cell Stem Cell. 2019 Mar 1. pii: S1934-5909(19)30013-X.