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Purity: ≥98%
Firsocostat (formerly also known as ND-630; GS-0976; NDI-010976; ND630) is a novel and potent inhibitor of ACC (acetyl-CoA carboxylase) with IC50 values of 2.1 and 6.1 nM for human ACC1 and ACC2, respectively. As a potent allosteric protein-protein interaction inhibitor, ND-630 interacts within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibits the enzymatic activity of both ACC isozymes, reduces fatty acid synthesis and stimulates fatty acid oxidation in cultured cells and in animals, and exhibits favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. When administered chronically to Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). Together, these data suggest that ACC inhibition by ND-630 may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and fatty liver disease.
| ln Vitro |
hACC1 (IC50=2.1±0.2 nM) and hACC2 (IC50=6.1±0.8 nM) are inhibited by firsocostat (ND-630). Reversible and extremely ACC-specific suppression exists. By interfering with the phosphopeptide receptor and dimerization sites of the enzyme, firsocostat inhibits the activity of ACC. With an EC50 of 66 nM, firsocostat inhibits the synthesis of fatty acids in HepG2 cells without altering the number of cells overall, the concentration of cellular proteins, or the binding of acetate and cholesterol [1].
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| ln Vivo |
When Firsocostat (ND-630) is given to diet-induced obese rats over an extended period of time, it improves insulin sensitivity, decreases hepatic steatosis, decreases weight gain without changing food intake, and has positive effects on dyslipidemia. Firsocostat Zucker Long-term Firsocostat administration decreased hepatic steatosis, enhanced insulin secretion in response to glucose, and decreased hemoglobin A1c (by 0.9%) in diabetic obese rats. In humans and rats, Firsocostat binds to plasma proteins at rates of 98.5% and 98.6%, respectively. The Sprague-Dawley male rats used in the pharmacokinetic evaluation of Firsocostat showed a plasma t1/2 of 4.5 hours, a bioavailability of 37%, and a clearance of 33 mL/min/kg. The volume of distribution was found to be 1.9 L/kg, and the maximum oral plasma concentration time was observed to be 0.25 hours[1].
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| References |
[1]. Harriman G, et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805
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| Molecular Formula |
C28H31N3O8S
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| Molecular Weight |
569.63
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| CAS # |
1434635-54-7
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| Related CAS # |
Firsocostat (S enantiomer);2128714-16-7
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| SMILES |
O=C(O)C(C)(C)N(C(N(C[C@@H](C1=CC=CC=C1OC)OC2CCOCC2)C3=C4C(C)=C(C5=NC=CO5)S3)=O)C4=O
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| Chemical Name |
(R)-2-(1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl)-2-methylpropanoic acid
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| Synonyms |
NDI-010976; NDI 010976; NDI010976; ND-630; ND 630; ND630; GS-0976; GS0976; GS 0976; firsocostat
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 0.5 mg/mL (0.88 mM) in 1% DMSO + 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (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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