IM156 | AMPK activator/Mitochondrial protein complex I inhibitor

IM156 (1422365-93-2) is a potent activator of AMP-activated protein kinase (AMPK) showing greater activity than metformin or AICAR.¹ It displayed protective effects in vivo against peritoneal¹, liver², renal³,and pulmonary fibrosis⁴. IM156 induces metabolic stress in Myc⁺ lymphoma cells by inhibiting TCA cycle metabolism and mitochondrial respiration (inhibits mitochondrial protein complex 1).⁴ IM156 acts as an antiproliferative in several cancer models.^5-7

References/Citations:

1. Ju et al. (2015), HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosis; Am. J. Physiol. Renal Physiol.,310 F342
2. Lee et al. (2016), AMP-activated protein kinase activator, HL156A reduces thioacetamide-induced liver fibrosis in mice and inhibits the activation of cultured hepatic stellate cells and macrophages; Int. J. Oncol., 49 1407
3. Tsogbadrakh et al. (2018), HL156A, a novel pharmacological agent with potent adenosine-monophosphate-activated protein kinase (AMPK) activator ameliorates renal fibrosis in a rat unilateral ureteral obstruction model; PLoS One, 13 e0201692
4. Izreig et al. (2020), Repression of LKB1 by mi-17`92 Sensitizes MYC-Dependent Lymphoma to Biguanidine Treatment; Cell Rep. Med., 1 100014
5. Choi et al. (2016), Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanidine (HL156A); Oncotarget, 7 65643
6. Jeong et al. (2020), Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells; Pharmaceuticals (Basel), 13 218
7. Geiger et al. (2022), First-in-human study of IM156, a novel potent biguanidine oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors; Invest. New Drugs, 40 1001