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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
AMPK; OXPHOS/oxidative phosphorylation
Lixumistat acetate targets AMPK (AMP-activated protein kinase), increasing AMPK phosphorylation. As a potent oxidative phosphorylation (OXPHOS) inhibitor, it modulates cellular energy metabolism. The compound is a metformin derivative with enhanced potency. |
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| ln Vitro |
Lixumistat (acetate) (0.31-10 μM) phosphorylates AMPKα1 Thr172 in NIH3T3 murine fibroblasts in a way that is dependent on both time and dose [1]. Acetate, or lixumistat, has no effect on the expression of important glucose homeostasis-related factors such phosphoenolpyruvate carboxykinase 1 (Pck1) or glucose-6-phosphatase (G6pase) [1].
Lixumistat acetate (0.31-10 μM) phosphorylates AMPKα1 Thr172 in NIH3T3 murine fibroblasts in a time- and dose-dependent manner. This activation of AMPK leads to downstream metabolic effects, including inhibition of OXPHOS. |
| ln Vivo |
In mice with diet-induced obesity, lixumistat (acetate) had no effect on metabolic regulation as measured by body weight, blood glucose, insulin levels, and lipid metabolic content [1]. Lixumistat (acetate) (50 mg/kg; for 2 months) has no effect on anxiety, weight, or mobility in general [2]. The aging-related reduction in spatial working memory and new object recognition memory can be considerably mitigated by lixumistat (acetate) [2]. Aged mice's hippocampal AMPK activity is markedly elevated by lixumistat (acetate) [2].
Lixumistat acetate attenuates aging-associated cognitive impairment in animal models. As an OXPHOS inhibitor, it can be used for the research of solid tumors. The compound is orally active, supporting its use in in vivo studies. |
| Enzyme Assay |
Metformin is a treatment of choice for patients with type 2 diabetes. Its action involves the phosphorylation of 5'-adenosine monophosphate activated protein kinase (AMPK), leading to inhibition of liver gluconeogenesis. The effects of a novel chemical compound derived from metformin, HL271, on molecular and physiological actions involving AMPK and rhythmically-expressed circadian clock genes were investigated. HL271 potently activated AMPK in a dose-dependent manner, and produced shortening of the circadian period and enhanced degradation of the clock genes PER2 and CRY1. Although the molecular effects of HL271 resembled those of metformin, it produced different physiological effects in mice with diet-induced obesity. HL271 did not elicit glucose-lowering or insulin-sensitizing effects, possibly because of altered regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1. This indicated that, although HL271 acted on circadian clock machinery through a similar molecular mechanism to metformin, it differed in its systemic effect on glucose and lipid metabolite regulations[1].
AMPK phosphorylation assays are performed using cell-based systems. Lixumistat acetate is incubated with cells, and AMPK phosphorylation at Thr172 is measured by Western blot or ELISA. Dose-response curves are generated to determine the compound's potency. |
| Cell Assay |
Western Blot analysis [1]
Cell Types: NIH3T3 cells Tested Concentrations: 0.31 μM, 0.62 μM, 1.25 μM, 2.5 μM, 5 μM, 10 μM Incubation Duration: 4 hrs (hours) Experimental Results: AMPK phosphorylation rate was Dramatically increased. Cell-based assays are conducted using NIH3T3 murine fibroblasts. Cells are treated with Lixumistat acetate at concentrations ranging from 0.31-10 μM, and AMPK phosphorylation is assessed. The compound's effects on OXPHOS and cellular metabolism are evaluated in cancer cell lines. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice (young group/12-16 weeks, old group/20-22 months) [2]
Doses: 50 mg/kg Route of Administration: Orally (drinking water), lasting 2 months Experimental Results: Attenuates age-related cognitive decline. Animal care and experimental procedures followed the guidelines of the Institutional Animal Care and Use Committee of the Institute of Basic Science (IBS). Experiments were performed with male and female C57BL/6J mice (12~16 weeks of age for the young group and 20~22 months of age for the old groups). Group-housed mice were separated into single cages for acclimatization one month before beginning drug treatment. Mice were housed under controlled temperature and light conditions (23℃, 12-h light:12-h dark cycle). Experiments were performed during the light phase. The old mice were divided into three groups and orally treated with normal drinking water (control), metformin solution (100 mg/kg), or HL271 solution (50 mg/kg) for 2 months.[2] In vivo studies are performed in animal models of aging-associated cognitive impairment and solid tumors. Lixumistat acetate is administered orally, and cognitive function, tumor growth, and metabolic parameters are assessed. |
| ADME/Pharmacokinetics |
Lixumistat acetate has a molecular weight of 375.35. It is soluble in DMSO and other organic solvents. Storage: powder at -20°C for up to 3 years; in solvent at -80°C for up to 2 years.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Lixumistat acetate are not extensively reported in the available literature. As a research compound, it is not intended for human use. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
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| Additional Infomation |
Risushita acetate is the acetate form of risushita, a highly bioavailable biguanide compound that is also an inhibitor of mitochondrial oxidative phosphorylation (OxPhos) with potential antitumor activity. After administration, risushita inhibits oxidative phosphorylation, reduces mitochondrial function, suppresses tumor cell metabolism, and deprives tumor cells of energy, thereby inhibiting tumor cell proliferation. Mitochondrial oxidative phosphorylation is overactivated in cancer cells and plays a crucial role in tumor cell proliferation. Drug-resistant tumor cells are highly sensitive to reduced mitochondrial oxidative phosphorylation because they struggle to compensate for the decline in mitochondrial function by increasing glycolysis.
Lixumistat acetate is a potent AMPK activator and OXPHOS inhibitor derived from Metformin. It is used for research on solid tumors and aging-associated cognitive impairment. The compound is not approved for clinical use and is supplied for research purposes only. |
| Molecular Formula |
C15H20F3N5O3
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|---|---|
| Molecular Weight |
375.3462
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| Exact Mass |
375.15
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| Elemental Analysis |
C, 48.00; H, 5.37; F, 15.18; N, 18.66; O, 12.79
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| CAS # |
1422365-94-3
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| Related CAS # |
Lixumistat hydrochloride;1422365-52-3;Lixumistat;1422365-93-2; 2043654-98-2 (mesylate); 2043654-97-1; 1422365-52-3 (HCl); 2043654-70-0 (malonate); 2043654-72-2 (furmate); 1422365-94-3 (acetate); 2043654-64-2 (TFA)
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| PubChem CID |
154573779
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
455
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(OC1C([H])=C([H])C(=C([H])C=1[H])/N=C(\N([H])[H])/N=C(\N([H])[H])/N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H])(F)F.O([H])C(C([H])([H])[H])=O
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| InChi Key |
AGFDCTOLSXWRDZ-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
N-(Imino((4-(trifluoromethoxy)phenyl)amino)methyl)-1-pyrrolidinecarboximidamide, acetate
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| Synonyms |
IM156 acetate Lixumistat IM-156 IM 156
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~266.42 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6642 mL | 13.3209 mL | 26.6418 mL | |
| 5 mM | 0.5328 mL | 2.6642 mL | 5.3284 mL | |
| 10 mM | 0.2664 mL | 1.3321 mL | 2.6642 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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