Dorsomorphin

Dorsomorphin (BML-275, Compound C) is a potent, selective and reversible AMPK inhibitor with Ki of 109 nM, shows no no significant activity on ZAPK, SYK, PKCθ, PKA and JAK3; inhibits AMPK activation induced by AICAR and Metformin, also inhibits bone morphogenetic protein (BMP) type I receptors (ALK2, ALK3 and ALK6) ; promotes cardiomyogenesis in mouse embryonic stem cells (ESCs) in vitro, induces autophagy in cancer cell lines via a mechanism independent of AMPK inhibition. (In Vitro) :Dorsomorphin (compound C) (0-10 μM, 18 h) suppresses 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner but has little effect on tunicamycin-induced GRP78 promoter activity. Dorsomorphin (compound C) C also suppresses GRP78 promoter activity induced by glucose withdrawal. Dorsomorphin (compound C) has no effect on 2DG-induced PERK activation and reduces the both basal and 2DG-induced AMPK phosphorylation levels in HT1080 cells. (In Vivo) :Dorsomorphin (compound C: 10 mg/kg, intravenously once) treatment leads to a 60% increase in total serum iron concentrations, reduces basal levels of hepcidin expression and increasing serum iron concentrations in adult mice.Dorsomorphin (compound C: 0.2 mg/kg, I.V., 30 min before LPS injection) reduces ICAM-1 and VCAM-1 expression in LPS-injected rat aorta.Dorsomorphin (compound C; 25 mg/kg; i.p. injection; in male BALB/c mice) treatment before lipopolysaccharide (LPS) injection significantly reduces lethality in contrast to animals treated with LPS challenge only.