| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
ACS itself is an enzyme rather than a drug, and its substrates serve as its "targets." Based on substrate specificity, ACS acts on fatty acids of varying chain lengths. Long-chain ACS primarily acts on C6 to C26 saturated and unsaturated long-chain fatty acids; the liver enzyme acts on acids from C6 to C20, while the brain enzyme shows activity up to C24. Additionally, ACS utilizes ATP and CoA as co-substrates, and its activity is subject to feedback regulation by cellular energy charge and the product acyl-CoA. In research, ACS is often targeted as a drug target for modulating lipid metabolism.
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|---|---|
| ln Vitro |
In vitro, the activity of ACS is determined by measuring the rate of its catalyzed reaction: fatty acid + ATP + CoA → AMP + PPi + acyl-CoA. Commercial ACS preparations (e.g., from Pseudomonas sp.) typically have a specific activity of ≥2 units/mg protein. One unit of activity is defined as the amount of enzyme required to produce 1.0 μmol of AMP (or oleoyl-CoA) per minute at pH 8.1 and 25°C. The enzyme shows activity on various fatty acids; for example, its relative activity on heptanoate is approximately 2.37 times that on octanoate.
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| ln Vivo |
In vivo, ACS activity is crucial for maintaining lipid metabolic homeostasis. Research indicates that ACS proteins are involved in regulating and facilitating the cellular uptake of long-chain fatty acids in mammalian cells. By activating fatty acids to acyl-CoAs, ACS not only provides substrates for β-oxidation but also supplies activated intermediates for the synthesis of triglycerides, phospholipids, and cholesteryl esters. Furthermore, in adipocytes, ACS interacts with fatty acid transport proteins to mediate the efficient transmembrane transport of long-chain fatty acids. The differential substrate preferences of ACS from various tissues reflect their specific physiological functions in those tissues.
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| Enzyme Assay |
Classic methods for in vitro ACS activity determination include continuous spectrophotometry or isotopic labeling. For spectrophotometry, a typical reaction system contains 50-100 mM Tris-HCl buffer (pH 8.1), 5-10 mM ATP, 0.5 mM CoA, 10 mM MgCl₂, 0.1-1 mM fatty acid substrate (e.g., oleate), and an appropriate amount of ACS enzyme. Since the direct products (AMP and PPi) are difficult to measure, a coupled system with pyruvate kinase (PK) and lactate dehydrogenase (LDH) is often used to convert generated AMP or PPi into NADH consumption, monitored at 340 nm. The reaction is carried out at 25-37°C, and enzyme activity is calculated from the initial linear rate.
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| Cell Assay |
To study ACS function at the cellular level, fatty acid uptake assays or lipid synthesis detection are commonly used. For a fatty acid uptake assay: seed adherent cells (e.g., hepatocytes or adipocytes) in 24-well plates and culture to confluence. Switch to serum-free medium for 2-4 hours to reduce endogenous fatty acid levels. Then add fluorescently or radioactively labeled (e.g., ³H or ¹⁴C) fatty acids (e.g., palmitate), along with an ACS inhibitor group (e.g., Triacsin C) and a vehicle control group. Incubate at 37°C for 0.5-2 hours. Stop the reaction with ice-cold buffer containing fatty acid-binding protein (e.g., BSA) and wash cells to remove surface-adsorbed free fatty acids. Lyse cells and quantify cellular uptake by scintillation counting or fluorescence detection, which indirectly reflects intracellular ACS activity.
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| Animal Protocol |
To study ACS function or evaluate its inhibitors in animal models, high-fat diet models or gene knockout mice are commonly used. For an inhibitor study example: select C57BL/6J mice and induce obesity and fatty liver by feeding a high-fat diet. After model establishment, randomly divide mice into a treatment group (administered ACS inhibitor such as Triacsin C via intraperitoneal injection or oral gavage at 2-10 mg/kg) and a control group (administered equal volume of vehicle). Administer once daily for 2-4 weeks. Monitor body weight, food intake, and blood glucose during the experiment. At the end, sacrifice animals and collect blood and liver tissue. Measure serum triglycerides and non-esterified fatty acids (NEFA) levels, and perform Oil Red O staining and lipid content determination on liver tissue to assess the impact of ACS inhibition on lipid metabolism.
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| ADME/Pharmacokinetics |
No direct systematic reports on the pharmacokinetic parameters of the ACS enzyme itself are available in the current literature, as ACS is a protein enzyme and not directly used as a drug. However, for small-molecule ACS inhibitors, their PK properties vary depending on the compound structure. ACS is primarily localized in the cytoplasm and the outer mitochondrial membrane, with high expression in metabolically active tissues such as the liver, adipose tissue, and brain. In studies on microbial ACS, the Michaelis constants (Km) are approximately 0.5 mM for ATP and 0.15 mM for octanoate. Since ACS is an endogenous enzyme, its "in vivo half-life" is primarily governed by protein turnover rates rather than traditional pharmacokinetics.
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| Toxicity/Toxicokinetics |
Detailed systematic toxicology data for Acyl coenzyme A synthetase (9013-18-7) are not available in the current public literature. According to product safety information from suppliers, this product is a biochemical reagent intended for research use only and is not approved for human therapeutic, diagnostic, or veterinary applications. During routine biochemical laboratory handling, standard safety precautions (such as wearing gloves, goggles, and a lab coat) should be followed, avoiding direct inhalation or skin contact. As an endogenous enzyme, ACS does not exhibit toxicity at physiological levels.
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| References |
[1]. Physiological role of Acyl coenzyme A synthetase homologs in lipid metabolism in Neurospora crassa. Eukaryot Cell. 2013 Sep;12(9):1244-57.
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| Exact Mass |
1802.613
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|---|---|
| CAS # |
9013-18-7
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| PubChem CID |
168009927
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
124
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| Complexity |
1180
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NYXALROAXMFXEX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/5C15H16ClNO.2C14H14ClNO/c3*1-8-5-9-6-13-10(12(9)7-14(8)16)3-2-4-11(13)15(17)18;2*1-8-5-9(16)6-13-10-3-2-4-11(15(17)18)14(10)7-12(8)13;2*15-9-5-4-8-6-13-10(12(8)7-9)2-1-3-11(13)14(16)17/h3*5,7,11H,2-4,6H2,1H3,(H2,17,18);2*5-6,11H,2-4,7H2,1H3,(H2,17,18);2*4-5,7,11H,1-3,6H2,(H2,16,17)
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| Chemical Name |
6-chloro-7-methyl-2,3,4,9-tetrahydro-1H-fluorene-1-carboxamide;6-chloro-8-methyl-2,3,4,9-tetrahydro-1H-fluorene-1-carboxamide;6-chloro-2,3,4,9-tetrahydro-1H-fluorene-1-carboxamide
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| Synonyms |
acyl-CoA synthetase; Acyl coenzyme A Synthetase; SCHEMBL29280531
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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 |
| 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 Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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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