| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
ACC (acetyl-CoA carboxylase)
Acetyl-CoA carboxylase (ACC) |
|---|---|
| ln Vitro |
The racemate itself has reduced potency compared to the pure R enantiomer due to the presence of the less active S form. The active R enantiomer (Firsocostat) exhibits IC50 values of 2.1 nM against ACC. In cell-based assays, Firsocostat inhibits fatty acid synthesis and promotes fatty acid oxidation in hepatocytes. The racemate is often used as a control or for comparative studies.
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| ln Vivo |
No specific in vivo data for the racemate alone; however, the active R enantiomer (Firsocostat) reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia in diet-induced obese rats when administered chronically. It also decreases hepatic steatosis and fibrosis markers in NASH patients.
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| Enzyme Assay |
The assay uses recombinant human ACC1 or ACC2 enzymes and measures the conversion of [14C]-acetyl-CoA to [14C]-malonyl-CoA in the presence of ATP, MgCl2, and the test compound. Reactions are incubated at 37degC for 10-30 minutes, then stopped by adding HCl. The product is extracted with organic solvent and quantified by scintillation counting. IC50 values are calculated from dose-response curves.
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| Cell Assay |
For cellular ACC inhibition, human hepatoma cell lines (e.g., Huh-7, HepG2) or primary human hepatocytes are cultured in high-glucose DMEM with 10% FBS. Cells are treated with the compound (0.1-1000 nM) for 4-24 hours. Fatty acid synthesis is measured by incorporation of [14C]-acetate into lipids, extracted with chloroform/methanol. ACC activity is assessed by quantifying malonyl-CoA levels using LC-MS/MS or by Western blot for ACC phosphorylation status.
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| Animal Protocol |
The active R enantiomer is administered orally (gavage) once or twice daily to diet-induced obese rats (5-30 mg/kg) for 2-12 weeks. Endpoints include serum triglycerides, hepatic lipid content (by histology or biochemical extraction), body weight, insulin sensitivity (HOMA-IR or OGTT), and gene expression of lipogenic enzymes (FASN, SCD1). Tissue ACC activity is measured ex vivo.
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| ADME/Pharmacokinetics |
Active R enantiomer: oral bioavailability in rodents >50%, plasma half-life ~2-4 hours, high plasma protein binding (>95%). Metabolized primarily by CYP3A4. For the racemate, pharmacokinetic parameters are likely similar to those of the active enantiomer, but with reduced efficacy due to the presence of the less active S enantiomer.
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| Toxicity/Toxicokinetics |
No specific toxicity data for the racemate; the active R enantiomer is generally well tolerated in preclinical studies at therapeutic doses (5-30 mg/kg). Higher doses may cause mild gastrointestinal disturbances (diarrhea, nausea) and reversible elevations in liver transaminases. No significant genotoxicity or cardiotoxicity reported in animal studies.
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| Additional Infomation |
Firsocostat (ND-630/GS-0976) advanced into clinical trials for NASH and hypertriglyceridemia. In Phase 2 trials, it reduced hepatic steatosis and fibrosis markers but development was discontinued due to modest efficacy and tolerability issues. The racemate (CAS: 2128714-16-7) is primarily a research reagent for comparative studies. Not approved for clinical use.
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| Molecular Formula |
C28H31N3O8S
|
|---|---|
| Molecular Weight |
569.626046419144
|
| Exact Mass |
569.183
|
| Elemental Analysis |
C, 59.04; H, 5.49; N, 7.38; O, 22.47; S, 5.63
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| CAS # |
2128714-16-7
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| Related CAS # |
Firsocostat;1434635-54-7
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| PubChem CID |
124672214
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| Appearance |
White to off-white solid powder
|
| LogP |
3.2
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
40
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| Complexity |
947
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=C(SC2=C1C(=O)N(C(=O)N2C[C@H](C3=CC=CC=C3OC)OC4CCOCC4)C(C)(C)C(=O)O)C5=NC=CO5
|
| InChi Key |
ZZWWXIBKLBMSCS-HXUWFJFHSA-N
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| InChi Code |
InChI=1S/C28H31N3O8S/c1-16-21-24(32)31(28(2,3)26(33)34)27(35)30(25(21)40-22(16)23-29-11-14-38-23)15-20(39-17-9-12-37-13-10-17)18-7-5-6-8-19(18)36-4/h5-8,11,14,17,20H,9-10,12-13,15H2,1-4H3,(H,33,34)/t20-/m1/s1
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| Chemical Name |
2-[1-[(2S)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid
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| Synonyms |
Firsocostat (racemate) (ND-630 racemate)
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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)
|
| Solubility (In Vitro) |
DMSO: ≥ 50 mg/mL (87.78 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 | 1.7555 mL | 8.7776 mL | 17.5553 mL | |
| 5 mM | 0.3511 mL | 1.7555 mL | 3.5111 mL | |
| 10 mM | 0.1756 mL | 0.8778 mL | 1.7555 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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