IM156 (HL156A; HL271 acetate) is a chemical derivative of Metformin. IM156 is a potent and orally active AMPK activator that increases AMPK phosphorylation. IM156 attenuates aging-associated cognitive impairment in animal model [1] [2]. IM156 is a potent oxidative phosphorylation (OXPHOS) inhibitor which is able to be used for the research of solid tumors [3].

IM156 (0.31-10 μM) phosphorylates AMPKα1 Thr172 in NIH3T3 mouse fibroblast cells in a dose- and time-dependent manner [1]. IM156 does not affect the expression of key factors involved in glucose homeostasis like glucose-6-phosphatase (G6pase) or phosphoenolpyruvate carboxykinase 1 (Pck1) [1]. Western Blot Analysis [1] Cell Line: NIH3T3 cells Concentration: 0.31 μM, 0.62 μM, 1.25 μM, 2.5 μM, 5 μM, 10 μM Incubation Time: 4 hours Result: Significantly increased the AMPK phosphorylation rate.

IM156 does not affect metabolic regulation assessed by body weight, blood glucose, insulin levels and lipid metabolite content in mice with diet-induced obesity [1]. IM156 (50 mg/kg; for 2 months) does not affect body weight, general locomotion, or anxiety [2]. IM156 markedly attenuates the aging-induced decline in novel object recognition memory and spatial working memory [2]. IM156 markedly increases AMPK activation in the hippocampus of aged mice [2]. Animal Model: C57BL/6J mice (young group/12-16 weeks, old groups/20-22 months) [2] Dosage: 50 mg/kg Administration: Oral administration (drinking water), for 2 months Result: Attenuated age-related cognitive decline.