NS-220

• CAT Number: I008363
• CAS Number: 377731-45-8
• Molecular Formula: C21H27NO5
• Molecular Weight: 373.45
• Purity: ≥95%
• Synonyms: NS-220; NS 220; NS220; LS-191458.;(2s,5s)-2-methyl-5-(4-(5-methyl-2-(p-tolyl)oxazol-4-yl)butyl)-1,3-dioxane-2-carboxylic acid
• Solubility: Soluble in DMSO
• Storage: Store at RT
• InChI: InChI=1S/C21H27NO5/c1-14-8-10-17(11-9-14)19-22-18(15(2)27-19)7-5-4-6-16-12-25-21(3,20(23)24)26-13-16/h8-11,16H,4-7,12-13H2,1-3H3,(H,23,24)/t16-,21+
• InChIKey: IMYPSTHZBIWMNA-NBEIKUQISA-N
• SMILES: O=C([C@@]1(C)OC[C@@H](CCCCC2=C(C)OC(C3=CC=C(C)C=C3)=N2)CO1)O

NS-220 is a novel selective peroxisome proliferator-activated receptor alpha agonist. It potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice.

Reference

1:J Pharmacol Exp Ther. 2004 Jun;309(3):970-7. Epub 2004 Feb 24. A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice.Kuwabara K,Murakami K,Todo M,Aoki T,Asaki T,Murai M,Yano J, PMID: 14982965 DOI: 10.1124/jpet.103.064659 Abstract: 2-Methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220) was newly synthesized and demonstrated to be a novel potent peroxisome proliferator-activated receptor alpha (PPARalpha) agonist with high subtype selectivity. In cell-based reporter gene assays, the EC(50) values of NS-220 for human PPARalpha, PPARgamma, and PPARdelta were 1.9 x 10(-8), 9.6 x 10(-6), and >10(-4) M, respectively, and for mouse PPARalpha, PPARgamma, and PPARdelta were 5.5 x 10(-8), 3.3 x 10(-5), and >10(-4) M, respectively. In addition, [(3)H]NS-220 bound to the ligand-binding domain of human PPARalpha with a K(D) value of 1.85 x 10(-7) M. Fenofibric acid and bezafibrate showed weak agonist activity for PPARalpha (EC(50), 2-8 x 10(-5) M), with poor subtype selectivity. NS-220 (0.1-3 mg/kg p.o.) decreased plasma triglyceride levels in ddY mice in a dose-dependent manner, but its hypolipidemic activity was abolished in PPARalpha-deficient mice. In KK-A(y) mice, an animal model of type-2 diabetes, NS-220 (0.3-1 mg/kg p.o.; 4 days) and fenofibrate (100-300 mg/kg p.o.; 4 days) decreased plasma triglyceride and glucose levels in a dose-dependent manner. In a 2-week repeated administration test, NS-220 (0.3-1 mg/kg p.o.) decreased plasma glucose levels markedly without increasing in plasma insulin levels. Furthermore, NS-220 increased high-density lipoprotein levels and decreased triglyceride-rich lipoprotein levels. In conclusion, a newly synthesized dioxanecarboxylic acid derivative, NS-220, is a potent and highly selective PPARalpha agonist that ameliorates metabolic disorders in diabetic mice. These results strongly suggest that it will be a promising drug for the treatment of hyperlipidemia or metabolic disorders in type-2 diabetes.