IM-156 is an inhibitor of mitochondrial complex I, also known as NADH dehydrogenase (IC₅₀= 2.2 µM) and an activator of AMP-activated protein kinase α (AMPKα).^1,2It reduces the oxygen consumption rate (OCR; IC₅₀= 3.3 µM) and decreases mitochondrial ATP production in Eµ-Mycmouse lymphoma cells.¹IM-156 (10, 30, and 50 µM) increases AMPKα activity in primary rat peritoneal mesothelial cells and protects against chlorhexidine-induced peritoneal fibrosis in rats when administered at a dose of 1 mg/kg.²It reduces tumor growth in an AT-84 murine oral cancer model and decreases age-related decline in novel object recognition, spatial working, and contextual memory in mice.^3,4

1.Izreig, S., Gariepy, A., Kaymak, I., et al.Repression of LKB1 by miR-17~92 sensitizes MYC-dependent lymphoma to biguanide treatmentCell Rep. Med.1(2)100014(2020) 2.Ju, K.D., Kim, H.J., Tsogbadrakh, B., et al.HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosisAm. J. Physiol. Renal. Physiol.310(5)F342-F350(2016) 3.Lam, T.G., Jeong, Y.S., Kim, S.-A., et al.New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathwaysCancer Sci.109(3)699-709(2018) 4.Bang, E., Lee, B., Park, J.-O., et al.The improving effect of HL271, a chemical derivative of metformin, a popular drug for type II diabetes mellitus, on aging-induced cognitive declineExp. Neurobiol.27(1)45-56(2018)