| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
ACSS2-IN-2 targets acyl-CoA synthetase short-chain family member 2 (ACSS2), an enzyme that catalyzes the conversion of acetate to acetyl-CoA. ACSS2 plays a critical role in cellular energy metabolism, lipid synthesis, and histone acetylation. It is particularly important in cancer cells that utilize acetate as an alternative carbon source under nutrient-deprived conditions. By inhibiting ACSS2 with high potency (IC50 = 3.8 nM), ACSS2-IN-2 disrupts acetate metabolism, which may have therapeutic implications for cancer, metabolic disorders, and other diseases.
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| ln Vitro |
In MDA-MB-468 cells, ACSS2-IN-2 (Compound 261) (5 hours) exhibits ACSS2 inhibitory activity with an IC50 value of 3.8 nM [1].
In vitro, ACSS2-IN-2 inhibits ACSS2 activity with an IC50 of 3.8 nM. The compound's potent ACSS2 inhibition makes it a valuable tool for studying the role of ACSS2 in cellular metabolism, histone acetylation, and disease pathogenesis. It can be used to investigate the contribution of acetate metabolism to cancer cell proliferation, viral replication, and inflammatory responses. Further cellular studies would be needed to characterize its effects on metabolism and gene expression. |
| ln Vivo |
In vivo, ACSS2-IN-2 has potential applications in various disease models, including viral infection, metabolic disorders, neuropsychiatric diseases, inflammatory/autoimmune conditions, and cancer. By inhibiting ACSS2, the compound may reduce acetate utilization, alter metabolic flux, and modulate inflammatory and immune responses. However, specific in vivo efficacy data for ACSS2-IN-2 have not been detailed in the available literature. Preclinical studies would be required to assess its therapeutic potential.
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| Enzyme Assay |
For in vitro enzyme assays, recombinant ACSS2 protein is incubated with acetate, CoA, and ATP in assay buffer. Enzyme activity is measured by monitoring the formation of acetyl-CoA or the production of AMP or pyrophosphate. The test compound is added at various concentrations (typically 0.001-100 nM). IC50 values are calculated by fitting dose-response curves of percent inhibition versus compound concentration.
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| Cell Assay |
For cell-based assays, cancer cells or other relevant cell types are treated with ACSS2-IN-2 at concentrations ranging from 0.01-10 µM for various time points. ACSS2 activity can be assessed by measuring cellular acetate metabolism using stable isotope-labeled acetate and LC-MS analysis. Histone acetylation levels can be measured by Western blotting with anti-acetyl-lysine or specific anti-acetyl-histone antibodies. Cell viability, proliferation, and metabolic flux can also be assessed.
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| Animal Protocol |
For in vivo studies, appropriate animal models of cancer, metabolic disorders, or inflammatory diseases would be used. ACSS2-IN-2 would be administered via oral or intraperitoneal routes at doses determined from pharmacokinetic studies. Disease progression, metabolic parameters, and inflammatory markers would be measured to assess efficacy. However, specific in vivo protocols for ACSS2-IN-2 have not been reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ACSS2-IN-2 have not been characterized in the available literature. The compound has a molecular weight of 415.39 g/mol, suggesting potential for drug-like properties. Standard PK studies including solubility, permeability, half-life, oral bioavailability, and tissue distribution would be required to support in vivo studies. The compound is typically stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Toxicological data for ACSS2-IN-2 have not been reported. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References |
[1]. Philippe Nakache, et al. Acss2 inhibitors and methods of use thereof. Patent. WO2019097515A1.
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| Additional Infomation |
ACSS2-IN-2 is a potent ACSS2 inhibitor with an IC50 of 3.8 nM. It can be used for research on viral infection, metabolic disorders, neuropsychiatric diseases, inflammatory/autoimmune conditions, and cancer. ACSS2-IN-2 inhibits the enzyme that converts acetate to acetyl-CoA, playing a role in cellular energy metabolism and histone acetylation. It is a research tool and is not approved for clinical use.
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| Molecular Formula |
C21H19F2N3O4
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|---|---|
| Molecular Weight |
415.390072107315
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| Exact Mass |
415.134
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| CAS # |
2332820-04-7
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| PubChem CID |
139443008
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
727
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NN(C(=O)C1C(=O)NC2=CC=CC(=C2)C(C)(F)F)C3=CC=CC(=C3)C(=O)OC
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| InChi Key |
CYQWPQYTOFVAIL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19F2N3O4/c1-12-17(18(27)24-15-8-5-7-14(11-15)21(2,22)23)19(28)26(25-12)16-9-4-6-13(10-16)20(29)30-3/h4-11,17H,1-3H3,(H,24,27)
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| Chemical Name |
methyl 3-[4-[[3-(1,1-difluoroethyl)phenyl]carbamoyl]-3-methyl-5-oxo-4H-pyrazol-1-yl]benzoate
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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 Vitro) |
DMSO : ~100 mg/mL (~240.74 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4074 mL | 12.0369 mL | 24.0738 mL | |
| 5 mM | 0.4815 mL | 2.4074 mL | 4.8148 mL | |
| 10 mM | 0.2407 mL | 1.2037 mL | 2.4074 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04990739
Conditions:Advanced Solid TumorProducts are for research use only; We do not sell to patients
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