ND-630

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ND-630

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	1434635-54-7
规格:	≥98%

包装与价格：

包装	价格(元)
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议

产品介绍

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.

理化性质和储存条件

Molecular Weight (MW)	569.63
Formula	C28H31N3O8S
CAS No.	1434635-54-7; ND-630 S enantiomer
Storage	-20℃ for 3 years in powder form
Storage	-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; NDI 010976; NDI010976; ND-630; ND 630; ND630; GS-0976; GS0976; GS 0976; firsocostat 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 SMILES Code: 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

实验参考方法

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.