IM156

IM156 (HL156A), a chemical derivative of metformin (HY-B0627), is a potent AMPK activator that increases AMPK phosphorylation. IM156 attenuates aging-associated cognitive impairment in animal model[1][2].

Signaling Pathways >> Epigenetics >> AMPK

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

Research Areas >> Neurological Disease

AMPK[1][2]

IM156 (0.31-10 μM) phosphorylates AMPKα1 Thr172 in a dose- and time-dependent manner in NIH3T3 mouse fibroblast cells[1]. IM156 does not affect the expression of key factors involved in glucose homeostasis such as 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 significantly attenuates the aging-induced decline in novel object recognition memory and spatial working memory[2]. IM156 significantly 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.

[1]. Row H, et al. HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism. Biochem Biophys Res Commun. 2016 Jan 15;469(3):783-9.

[2]. Bang E, et al. The Improving Effect of HL271, a Chemical Derivative of Metformin, a Popular Drug for Type II Diabetes Mellitus, on Aging-induced Cognitive Decline. Exp Neurobiol. 2018 Feb;27(1):45-56.