产品说明书

Firsocostat

Print
Chemical Structure| 1434635-54-7 同义名 : ND-630;GS-0976;ND630. NDI-010976;NDI-010976
CAS号 : 1434635-54-7
货号 : A512642
分子式 : C28H31N3O8S
纯度 : 99%+
分子量 : 569.626
MDL号 : MFCD28963986
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(87.78 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Fatty acid metabolism dysregulated through elevated fatty acid synthesis (FASyn), impaired fatty acid oxidation (FAOxn), or both is a hallmark of various metabolic disorders. ACC (acetyl-CoA carboxylase) catalyzes the ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA, the rate-limiting and first committed reaction in FASyn. ND-630, a reversible and highly specific ACC inhibitor, inhibits hACC1 with an IC50 of 2.1 ± 0.2 nM and hACC2 with an IC50 of 6.1 ± 0.8 nM. When ND-630 and [14C]acetate were administered to Hep-G2 cells for 4 h, ND-630 inhibited FASyn with EC50 values of 66 nM in cells cultured in medium containing 10% serum and 8.7 nM when assessed in serum-free medium. When ND-630 and [14C]palmitate were administered to C2C12 cells for 6 h, ND-630 increased both the release of [14C]O2 and the production of [14C]acid-soluble material. ND-630 exhibited an aqueous solubility of 594 μM and human and rat plasma protein binding of 98.5% and 98.6%, respectively. When chow-fed male Sprague–Dawley rats were treated orally with ND-630 for 1 h, hepatic malonyl-CoA was dose-dependently reduced with an ED50 of 0.8 mg/kg. When chow-fed male Sprague–Dawley rats treated orally with ND-630 for 1 h were given an i.p. bolus of [14C]acetate, ND-630 reduced hepatic FASyn with an ED50 of 0.14 mg/kg. Moreover, ND-630 increased whole-body FAOxn, assessed as a reduction in respiratory quotient (RQ). As a consequence of FASyn inhibition and FAOxn stimulation, ND-630 dose-dependently reduced the hepatic steatosis produced by the HSD (high-sucrose diet) without altering either hepatic cholesterol or glycogen. ND-630 also dose-dependently reduced the elevated plasma triglycerides and free fatty acids produced by the HSD[1].
作用机制 ND-630 interacts within the acetyl-CoA carboxylase subunit phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit enzymatic activity[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.76mL

0.35mL

0.18mL

8.78mL

1.76mL

0.88mL

17.56mL

3.51mL

1.76mL
参考文献

[1]Harriman G, Greenwood J, Bhat S, 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;113(13):E1796-E1805.