DMX-5804

DMX-5804 is a potent, orally active and selective MAP4K4 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[1].

Signaling Pathways >> MAPK/ERK Pathway >> MAP4K

Research Areas >> Cardiovascular Disease

MAP4K4:3 nM (IC50)

MAP4K4:8.55 (pIC50)

MINK1/MAP4K6:8.18 (pIC50)

TNIK/MAP4K7:7.96 (pIC50)

GCK/MAP4K2:6.50 (pIC50)

KHS/MAP4K5:6.36 (pIC50)

GLK/MAP4K3:4.95 (pIC50)

MLK1/MAP3K9:7.19 (pIC50)

MLK3/MAP3K11:6.99 (pIC50)

NUAK:6.88 (pIC50)

VEGFR:5.72 (pIC50)

ABL1:5.80 (pIC50)

Aurora B:5.49 (pIC50)

FLT3:5.31 (pIC50)

GSK3β:4.66 (pIC50)

DMX-5804 exhibits great selectivity at MAP4K4 over other kinases, such as GCK/MAP4K2 (pIC50, 6.50), GLK/MAP4K3 (pIC50, 4.95), KHS/MAP4K5 (pIC50, 6.36), ABL1 (pIC50, 5.80), Aurora B (pIC50, 5.49), FLT3 (pIC50, 5.31), GSK3β (pIC50, 4.66), MLK1/MAP3K9 (pIC50, 7.19), MLK3/MAP3K11 (pIC50, 6.99), NUAK (pIC50, 6.88) and VEGFR (pIC50, 5.72)[1].

[1]. Fiedler LR, et al. MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo. Cell Stem Cell. 2019 Mar 1. pii: S1934-5909(19)30013-X.