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Beschreibung

A cell-permeable benzimidazole that, in addition to its inhibitory potency against luciferase activity (IC50<10 nM), is reported to activate AMPK signaling by increasing cellular ADP/ATP ratio via mitochondria respiration uncoupling in a cell type-specific manner, effectively activating AMPK & PGC-1alpha in muscle, but not liver, cell types both in cultures (5-20 µ,M & 1-24 h in rat L6 myotubes, no effect in primary rat hepatocytes) in vitro and in db/db mice (gastrocnemius/calf muscle, but not liver tissue, 15 mg/kg/day via p.o. for 6 wks) in vivo. ZLN005 is orally available in mice (plasma Cmax & Tmax = 3.7 µ,M & 15 min, respectively, following single 15 mg/kg oral dosage to db/db mice) and is efficacious in improving glucose (1.5 g/kg i.p.) tolerance among 4-wk-treated and insulin (1 unit/kg) tolerance among 5-wk treated db/db mice (by 14% and 18%, respectively, 15 mg/kg/day via p.o.) in vivo without any apparent effects on body weight or food intake among db/db or non-diabetic controls., A cell-permeable benzimidazole that, in addition to its inhibitory potency against luciferase activity (IC50<10 nM), also activates AMPK signaling by increasing cellular ADP/ATP ratio via mitochondria respiration upcoupling, effectively activating AMPK & PGC-1alpha in muscle, but not liver, cell types both in cultures (5-20 µ,M in rat L6 myotubes) in vitro and in db/db mice (15 mg/kg/day via p.o.) in vivo. Reported to improve glucose and insulin tolerance of db/db mice without any apparent effects on body weight or food intake.