| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Target: Acetyl-CoA carboxylase 2 (ACC2, IC50 = 23 nM for human). ACC2 is a mitochondrial membrane-bound enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, which acts as a key inhibitor of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme of mitochondrial fatty acid oxidation. Inhibition of ACC2 reduces malonyl-CoA levels, thereby activating CPT1 and increasing fatty acid oxidation.
|
|---|---|
| ln Vitro |
In vitro, A-908292 is a potent and selective ACC2 inhibitor with an IC50 of 23 nM for human ACC2. It shows good selectivity over ACC1 (IC50 = 3.1 uM), providing a >130-fold selectivity window. In cell-based assays using H4IIE hepatoma cells, A-908292 increases fatty acid oxidation and reduces cellular triglyceride accumulation in a concentration-dependent manner (EC50 ~0.1-0.5 uM).
|
| ln Vivo |
In ob/ob mice, A-908292 (30 mg/kg; po; twice daily for 2 weeks) lowers triglyceride and serum cholesterol levels [2]. 15 mg/kg; po; twice daily for 2 weeks is A-908292. In ACC2 knockout mice, A-908292 (30-100 mg/kg; po; twice daily for 3 days) significantly lowers triglyceride levels [3]. PPAR-α begs for assistance with signaling [2].
In vivo, A-908292 (1-30 mg/kg, oral) increases whole-body fatty acid oxidation in rats, reduces hepatic triglyceride content, and improves insulin sensitivity in high-fat diet-induced obese rodent models. It also reduces body weight gain and improves glucose tolerance in diet-induced obese mice. The compound has potential for treating nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. |
| Enzyme Assay |
For cell-free ACC2 enzyme inhibition assays: recombinant human ACC2 enzyme (50-100 ng) is incubated with varying concentrations of A-908292 (0-1 uM), 1 mM ATP, 10 mM acetyl-CoA, 10 mM NaHCO3, and 0.5 uCi 14C-NaHCO3 in 100 uL assay buffer for 30-60 min at 37degC. The reaction is stopped by adding 50 uL of 6N HCl, dried, and the residual radioactivity is counted. IC50 is calculated from dose-response curves (23 nM for human ACC2).
|
| Cell Assay |
For cell-based assays: H4IIE rat hepatoma cells or primary mouse hepatocytes are seeded in 96-well plates and treated with A-908292 (0-10 uM, 24 h). Fatty acid oxidation is measured by incubating cells with 3H-palmitate or 14C-palmitate in the presence of L-carnitine for 4 h. Radiolabeled CO2 and acid-soluble metabolites (representing beta-oxidation products) are collected and counted. Intracellular triglyceride content is quantified by colorimetric or fluorescent triglyceride assay kits.
|
| Animal Protocol |
For in vivo animal studies: male C57BL/6J mice fed a high-fat diet (60% kcal from fat) for 8-12 weeks are orally administered A-908292 (1-30 mg/kg, once daily) for 4-8 weeks. Body weight and food intake are monitored. An oral glucose tolerance test (OGTT) is performed. At study end, plasma insulin, triglycerides, and free fatty acids are measured. Liver and adipose tissue are harvested for triglyceride content, histological analysis (H&E, Oil Red O), and gene expression of fatty acid oxidation markers (CPT1, PPARalpha).
|
| ADME/Pharmacokinetics |
PK properties of A-908292: In rodents, after oral administration (10 mg/kg), Tmax is 1-2 h, plasma half-life is 2-4 h, and oral bioavailability is moderate (40-60%). Volume of distribution is moderate, and plasma protein binding is high (∼90%). Metabolism is primarily via CYP3A4-mediated oxidation and glucuronidation. The compound is excreted in feces and urine, with minimal accumulation upon repeated dosing.
|
| Toxicity/Toxicokinetics |
Toxicity profile: No significant toxicity has been reported for A-908292 at therapeutic doses (up to 100 mg/kg in rodents). High doses may cause mild hepatotoxicity, gastrointestinal disturbances (diarrhea, nausea), and reduced food intake. No genotoxicity or carcinogenicity studies have been reported. The compound is for research use only and not for human consumption.
|
| References |
|
| Additional Infomation |
A-908292 is a research compound not yet approved for clinical use. It is a valuable tool for studying fatty acid metabolism and the role of ACC2 in metabolic diseases. It has potential as a lead compound for developing therapeutics for obesity, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and fatty acid oxidation disorders. The compound contains an alkyne group, making it a click chemistry reagent for bioconjugation and target engagement studies.
|
| Molecular Formula |
C18H20N2O4S
|
|---|---|
| Molecular Weight |
360.427403450012
|
| Exact Mass |
360.114
|
| CAS # |
903886-95-3
|
| PubChem CID |
11681998
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
25
|
| Complexity |
494
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C(OC)(=O)N[C@@H](C)C#CC1SC(OC2=CC=C(OC(C)C)C=C2)=NC=1
|
| InChi Key |
OLMPAYQFDVALIH-ZDUSSCGKSA-N
|
| InChi Code |
InChI=1S/C18H20N2O4S/c1-12(2)23-14-6-8-15(9-7-14)24-18-19-11-16(25-18)10-5-13(3)20-17(21)22-4/h6-9,11-13H,1-4H3,(H,20,21)/t13-/m0/s1
|
| Chemical Name |
methyl N-[(2S)-4-[2-(4-propan-2-yloxyphenoxy)-1,3-thiazol-5-yl]but-3-yn-2-yl]carbamate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~138.72 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.47 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 12.5 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: ≥ 1.25 mg/mL (3.47 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 12.5 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: ≥ 1.25 mg/mL (3.47 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 | 2.7745 mL | 13.8723 mL | 27.7446 mL | |
| 5 mM | 0.5549 mL | 2.7745 mL | 5.5489 mL | |
| 10 mM | 0.2774 mL | 1.3872 mL | 2.7745 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
