HL271, a derivative of metformin, is a potent AMPK activator that increases AMPK phosphorylation. HL271 attenuates aging-associated cognitive impairment.

HL271 does not affect the expression of key factors involved in glucose homeostasis such as glucose-6-phosphatase (G6pase) or phosphoenolpyruvate carboxykinase 1 (Pck1).HL271 (0.31-10 μM) phosphorylates AMPKα1 Thr172 in a dose- and time-dependent manner in NIH3T3 mouse fibroblast cells.

HL271 significantly attenuates the aging-induced decline in novel object recognition memory and spatial working memory. HL271 significantly increases AMPK activation in the hippocampus of aged mice.HL271 does not affect metabolic regulation assessed by body weight, blood glucose, insulin levels and lipid metabolite content in mice with diet-induced obesity.?HL271 (50 mg/kg;?for 2 months) does not affect body weight, general locomotion, or anxiety.