| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| Molecular Weight (MW) | 569.63 |
|---|---|
| Formula | C28H31N3O8S |
| CAS No. | 1434635-54-7 (R-isomer) |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: > 50 mg/mL |
| Water: < 1mg/mL | |
| Ethanol: < 1mg/mL | |
| 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 |
| Synonyms | NDI-010976 S-isomer; NDI 010976; NDI010976; ND-630 S-isomer; ND 630; ND630; GS-0976; GS0976; GS 0976; firsocostat S-isomer |
| In Vitro | In vitro activity: ND-630 (also known as GS-0976; NDI-010976; firsocostat) is a potent inhibitor of ACC (acetyl-CoA carboxylase). 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. ND-630 inhibits hACC1 (IC50=2.1±0.2 nM) and hACC2 (IC50=6.1±0.8 nM). Inhibition is reversible and highly specific for ACC. ND-630 inhibits ACC activity by interacting within the phosphopeptide-acceptor and dimerization site of the enzyme to prevent dimerization. ND-630 inhibits fatty acid synthesis with an EC50 of 66 nM in HepG2 cells without altering the total cell number, cellular protein concentration, and incorporation of acetate into cholesterol. Kinase Assay: ND-630 inhibits human ACC1 and ACC2 with IC50 values of 2.1 and 6.1 nM, respectively. Cell Assay: ND-630 interacts within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. |
|---|---|
| In Vivo | Chronical administration of ND-630 to rats with diet-induced obesity reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia. Chronical administration of ND-630 Zucker diabetic fatty rats, ND-630 reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c (0.9% reduction). ND-630 exhibits an aqueous solubility of 594 μM and human and rat plasma protein binding of 98.5% and 98.6%, respectively. Pharmacokinetic evaluation of ND-630 in male Sprague–Dawley rats [i.v. 3 mg/kg; orally (p.o.) 10 mg/kg] yields a plasma t1/2 of 4.5 h, bioavailability of 37%, clearance of 33 mL/min/kg, volume of distribution of 1.9 L/kg, oral time of maximum plasma concentration of 0.25 h. |
| Animal model | Zucker diabetic fatty rats |
| Formulation & Dosage | ND-630 is formulated in aqueous saline solution containing 1% Tween 80 and 0.5% methyl cellulose; 0.5, 1.5, 5 mg/kg; Oral gavage b.i.d. for 37 d. |
| References | Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805. |
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