S-2E
目录号 : GC67661
S-2E 是一种具有口服活性且非竞争性的 HMG-CoA 还原酶和乙酰-CoA 羧化酶 (acetyl-CoA carboxylase) 抑制剂。S-2E 具有抗高血脂作用，可用于家族性高胆固醇血症和混合性高脂血症的研究。
Cas No.:155730-92-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
S-2E is an orally active and noncompetitive HMG-CoA reductase and acetyl-CoA carboxylase inhibitor. S-2E has an anti-hyperlipidemic action. S-2E has the potential for familial hypercholesterolemia and mixed hyperlipidemia research[1][2].
In the liver, S-2E is converted into its active metabolite, S-2E-CoA. S-2E-CoA noncompetitively inhibits the enzymatic activities of both 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and acetyl-CoA carboxylase at Ki=18.11 μM and Ki=69.2 μM, respectively[1].
S-2E (3-30 mg/kg) given orally suppresses the secretion rate of very-low-density lipoprotein (VLDL)-cholesterol and triglyceride in Triton WR-1339-injected rats. Furthermore, S-2E lowers the blood total cholesterol and triglyceride levels simultaneously in Zucker fatty rats[1].
[1]. Koichi Ohmori, et al. Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative, S-2E. Eur J Pharmacol. 2003 Jun 13;471(1):69-76.
[2]. K Ohmori, et al. Effects of a novel antihyperlipidemic agent, S-2E, on the blood lipid abnormalities in homozygous WHHL rabbits. Metabolism. 2004 May;53(5):680-5.
| Cas No. | 155730-92-0 | SDF | Download SDF |
| 分子式 | C22H25NO4 | 分子量 | 367.44 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7215 mL | 13.6077 mL | 27.2153 mL |
| 5 mM | 0.5443 mL | 2.7215 mL | 5.4431 mL |
| 10 mM | 0.2722 mL | 1.3608 mL | 2.7215 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative, S-2E
Eur J Pharmacol 2003 Jun 13;471(1):69-76.PMID:12809954DOI:10.1016/s0014-2999(03)01793-x.
A newly synthesized benzoic acid derivative, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]methoxybenzoic acid (S-2E), has the capacity to inhibit the biosynthesis of both sterol and fatty acids. Here, we report the mechanism by which S-2E lowers blood cholesterol and triglyceride levels. In the liver, S-2E was converted into its active metabolite, S-2E-CoA. S-2E-CoA noncompetitively inhibited the enzymatic activities of both 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and acetyl-CoA carboxylase at K(i)=18.11 microM and K(i)=69.2 microM, respectively. Interestingly, pharmacokinetic experiments in rats showed that the concentration of S-2E-CoA in the liver was sufficient to inhibit the activities of HMG-CoA reductase and acetyl-CoA carboxylase, for example, when orally given to rats at 10 mg/kg. Indeed, S-2E (3-30 mg/kg) given orally suppressed the secretion rate of very-low-density lipoprotein (VLDL)-cholesterol and triglyceride in Triton WR-1339-injected rats. Furthermore, S-2E lowered the blood total cholesterol and triglyceride levels simultaneously in Zucker fatty rats. Collectively, S-2E may be useful in the treatment of familial hypercholesterolemia and mixed hyperlipidemia.
Effects of a novel antihyperlipidemic agent, S-2E, on the blood lipid abnormalities in homozygous WHHL rabbits
Metabolism 2004 May;53(5):680-5.PMID:15131777DOI:10.1016/j.metabol.2003.11.024.
To improve mixed hyperlipidemia in the low-density lipoprotein (LDL) receptor-deficient state, suppression of very-low-density lipoprotein (VLDL) particle production may be an important approach. We previously reported that S-2E, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl] methoxybenzoic acid, suppressed VLDL particle production by inhibiting the biosynthesis of both sterol and fatty acids in the liver. We therefore examined whether S-2E lowered the blood cholesterol and triglyceride (TG) levels simultaneously in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, which correspond to human familial hypercholesterolemia. S-2E given orally at doses of 30 to 300 mg/kg significantly lowered serum total cholesterol (TC) levels at 1 week as well as TG at 2 weeks, and the lowering of TC and TG levels by S-2E reached a maximum at 3 to 4 weeks. In contrast, oral administration of pravastatin at doses of 10 to 100 mg/kg resulted in a significant suppression of TC levels (100 mg/kg) but not TG levels. Further analysis of the TC content in fractionated serum of control and S-2E-treated animals showed that suppression of TC level by S-2E is attributable to a decrease in the proportions of VLDL, intermediate-density lipoprotein (IDL), and LDL. It is, therefore, reasonable to assume that S-2E may be useful to improve the blood lipid abnormalities in the LDL receptor-deficient state.
Effects of a novel anti-hyperlipidemic agent, S-2E, on blood lipid levels in rats with fructose-induced hypertriglyceridemia
Pharmacology 2004 Dec;72(4):240-6.PMID:15539884DOI:10.1159/000080379.
Using rats with fructose-induced hypertriglyceridemia, an animal model of human hypertriglyceridemia, we investigated whether (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]-methoxybenzoic acid (S-2E), a novel anti-hyperlipidemic agent, reduced the elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C), and then whether it elevated HDL-C levels. At doses of 3-30 mg/kg, S-2E reduced elevated TG levels and non-HDL-C levels simultaneously in a dose-dependent manner after a week. Furthermore, S-2E treatment at 10 mg/kg for 4 weeks showed similar effects, while the elongation of intervals between feeding periods led to further increases in these levels. Interestingly, S-2E increased blood HDL-C levels after 4 weeks of treatment. It is therefore reasonable to assume that S-2E may be useful to improve dyslipidemia such as hypertriglyceridemia and low levels of HDL-C.
Synthesis of the optical isomers of 4-[1-(4-tert-butylphenyl)-2-oxo- pyrrolidine-4-yl]methyloxybenzoic acid (S-2) and their biological evaluation as antilipidemic agent
Chem Pharm Bull (Tokyo) 1999 Nov;47(11):1549-54.PMID:10605053DOI:10.1248/cpb.47.1549.
The enantiomers of (+/-)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2), a new antilipidemic agent having dual action on the plasma triglyceride (TG) and cholesterol (Cho) lowering effects, were prepared via separation by Chiralcel OJ column chromatography of their methyl ester and also by the same method as the described racemate's synthesis from optically active 1-(4-tert-butylphenyl)-2-oxo-pyrrolidine-4-carboxylic acid respectively. These optically active carboxylic acids were prepared by the resolution of diastereomeric N-[(S)-(-)-[4-methyl-(alpha-methyl)benzyl]]-1-(4-tert-butylphenyl)-2-oxo - pyrrolidine-4-carboxyamide using silica gel column chromatography, followed by deamination with N2O4. The absolute configurations for the enantiomers of S-2 were indirectly determined using X-ray analysis of the 4-bromo-2-fluorobenzamide of the (+)-4-[1-(4-tert-butylphenyl)-2- oxo-pyrrolidine-4-yl]-methyloxybenzoic acid. S-2 and its enantiomers showed an essentially equipotent activity on the fatty acid- and sterol-biosynthesis inhibition in vitro. On the other hand, in the in vivo activity, (S)-(+)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine- 4-yl]methyloxybenzoic acid (S-2E) was superior in the lowering abilities of the plasma TG and phospholipid(PL) and was chosen as a candidate for a novel antilipidemic agent. The difference in the in vivo activity among S-2 and its enantiomers was explained from the pharmacokinetics after administration p.o.
The Novel Lipid-Lowering Drug D-47 Ameliorates Hepatic Steatosis and Promotes Brown/Beige-Like Change of White Adipose Tissue in db/db Mice
Kobe J Med Sci 2019 Jun 17;65(1):E36-E43.PMID:31341155doi
D-47 is a newly developed solid dispersion of the arginine salt of (S)-(+)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidin-4-yl]methoxybenzoic acid (S-2E), which inhibits sterol and fatty acid synthesis. D-47 was recently shown to lower the serum level and hepatic content of both triglyceride and cholesterol in a rabbit model of familial hypercholesterolemia. We here investigated the effects of D-47 on dyslipidemia and hepatic steatosis in comparison with those of bezafibrate in the db/db mouse model of obesity. Treatment of db/db mice with D-47 or bezafibrate for 14 days lowered the serum triglyceride concentration without affecting that of cholesterol. D-47, but not bezafibrate, almost completely eliminated lipid droplets in hepatocytes and markedly lowered the triglyceride content of the liver in these mice. The two agents induced similar changes in the hepatic expression of genes including those related to β-oxidation or fatty acid synthesis. D-47 however significantly reduced the mass of white adipose tissue and up-regulated the expression of genes related to energy expenditure, mitochondrial function, fatty acid oxidation or lipolysis in this tissue, indicating that D-47 induced the brown/beige adipocyte-like change in white adipose tissue, whereas bezafibrate had no such effects. Treatment of 3T3-L1 adipocytes with D-47 provoked the expression of genes related to mitochondrial function, fatty acid oxidation or lipolysis. Our data have thus shown that D-47 ameliorated hypertriglyceridemia and hepatic steatosis in an animal model of obesity, and they suggest that this latter effect might be mediated through the change of adipose tissue characteristics.