Lixumistat acetate

• CAT Number: I029233
• CAS Number: 1422365-94-3
• Molecular Formula: C15H20F3N5O3
• Molecular Weight: 375.35
• Purity: ≥95%
• Synonyms: acetic acid;N’-[N’-[4-(trifluoromethoxy)phenyl]carbamimidoyl]pyrrolidine-1-carboximidamide
• InChI: InChI=1S/C13H16F3N5O.C2H4O2/c14-13(15,16)22-10-5-3-9(4-6-10)19-11(17)20-12(18)21-7-1-2-8-21;1-2(3)4/h3-6H,1-2,7-8H2,(H4,17,18,19,20);1H3,(H,3,4)
• InChIKey: AGFDCTOLSXWRDZ-UHFFFAOYSA-N
• SMILES: CC(=O)O.C1CCN(C1)C(=NC(=NC2=CC=C(C=C2)OC(F)(F)F)N)N

Lixumistat (IM156; HL156A; HL271) acetate, a chemical derivative of Metformin (HY-B0627), is a potent and orally active AMPK activator that increases AMPK phosphorylation. Lixumistat (acetate) attenuates aging-associated cognitive impairment in animal model[1][2]. Lixumistat (acetate) is a potent oxidative phosphorylation (OXPHOS) inhibitor which can be used for the research of solid tumors[3].
Lixumistat (acetate) (0.31-10 μM) phosphorylates AMPKα1 Thr172 in a dose- and time-dependent manner in NIH3T3 mouse fibroblast cells[1].
Lixumistat (acetate) does not affect the expression of key factors involved in glucose homeostasis such as glucose-6-phosphatase (G6pase) or phosphoenolpyruvate carboxykinase 1 (Pck1)[1].
Lixumistat (acetate) does not affect metabolic regulation assessed by body weight, blood glucose, insulin levels and lipid metabolite content in mice with diet-induced obesity[1].
Lixumistat (acetate) (50 mg/kg; for 2 months) does not affect body weight, general locomotion, or anxiety[2].
Lixumistat (acetate) significantly attenuates the aging-induced decline in novel object recognition memory and spatial working memory[2].
Lixumistat (acetate) significantly increases AMPK activation in the hippocampus of aged mice[2].

Reference

[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.
 [Content Brief]

[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.
 [Content Brief]

[3]. Sun Young Rha, et al. Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors. Journal of Clinical Oncology 38(15_suppl):3590-3590.