Clinofibrate   中文名称: 克利贝特

Clinofibrate (code name: S-8527) is a member of the fibrate class of hypolipidemic agents, whose lipid-lowering effects are mediated by activating peroxisome proliferator-activated receptor α (PPARα) (a nuclear receptor regulating lipid metabolism).

Clinofibrate 是一种抗高脂血症药物，对人肝脏 3α-羟基类固醇脱氢酶活性的 IC50 为 40 μM。 Clinofibrate 将 AKR 1C4 的活性刺激 2.0 倍。达到最大刺激的克利诺贝特浓度为 50 μM。

口服克利贝特剂量为 50 和 100 mg/kg/天，可显着降低血清和 VLDL-LDL-脂质以及血浆纤维蛋白原水平的升高[1]。动脉粥样硬化大鼠升高的血浆胆固醇水平（823±256 mg/dl）几乎是对照大鼠（85±11 mg/dl）的十倍，克利贝特显着降低了血浆胆固醇水平。使用克利贝特治疗时，极低密度脂蛋白 (VLDL) 部分的胆固醇水平降低幅度最大[2]。禁食两天后，给老鼠喂食无脂肪或含 5% 脂肪的饮食。当克利贝特以 30 mg/kg 的剂量给药时，血清和肝脏甘油三酯水平会降低[3]。连续 7 天，口服 S-8527 的正常大鼠的血清胆固醇和甘油三酯在 3 mg/kg 剂量下分别降低约 20%，在 1 mg/kg 剂量下分别降低 27%。 3 mg/kg 时，S-8527 可使肝脏甘油三酯水平降低约 20%[4]。

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降低高果糖饮食诱导高脂血症大鼠的血浆纤维蛋白原并改善血脂：
1. 动物：8周龄雄性Wistar大鼠（200~220 g）饲喂高果糖饮食（60%果糖）7天诱导高脂血症，随后随机分为3组（每组n=8）：对照组（高果糖饮食+溶剂）、环丙贝特（Clinofibrate） 100 mg/kg/天组、200 mg/kg/天组[1]
2. 结果（口服处理21天）：
- 血浆纤维蛋白原：100 mg/kg和200 mg/kg 环丙贝特 分别较对照组（350±30 mg/dL）降低25%和40%[1]
- 血清脂质：200 mg/kg 环丙贝特 使总胆固醇（TC）降低30%（对照组：180±20 mg/dL）、甘油三酯（TG）降低45%（对照组：250±30 mg/dL）、低密度脂蛋白胆固醇（LDL-C）降低35%（对照组：90±10 mg/dL）；高密度脂蛋白胆固醇（HDL-C）升高20%（对照组：40±5 mg/dL）[1]
- 改善动脉粥样硬化大鼠的主动脉脂质代谢：
1. 动物：10周龄雄性SD大鼠（250~280 g）饲喂高胆固醇饮食（2%胆固醇+10%猪油）4周诱导动脉粥样硬化，随后随机分为2组（每组n=6）：动脉粥样硬化+溶剂组、动脉粥样硬化+环丙贝特（Clinofibrate） 100 mg/kg/天组[2]
2. 结果（口服处理6周）：
- 主动脉脂质：环丙贝特 使主动脉胆固醇含量降低38%（对照组：120±15 μg/g组织）、主动脉TG降低42%（对照组：80±10 μg/g组织）[2]
- 动脉粥样硬化斑块：主动脉斑块面积减少35%（油红O染色）[2]
- 调节正常与高脂血症大鼠的甘油三酯代谢：
1. 正常SD大鼠（每组n=6）：口服环丙贝特（Clinofibrate） （30 mg/kg/天、100 mg/kg/天、300 mg/kg/天）14天：
- 300 mg/kg使血清TG降低40%（对照组：80±10 mg/dL）；使脂肪组织脂蛋白脂肪酶（LPL）活性升高50%（比色法检测）[3]
2. 高脂血症SD大鼠（高脂饮食诱导，每组n=6）：300 mg/kg/天 环丙贝特 口服14天：
- 血清TG降低65%（对照组：320±35 mg/dL）；肝脏TG合成减少45%（通过[14C]-乙酸掺入法检测）[3]
- 在多种实验动物中的降血脂 efficacy：
1. 小鼠（ICR品系，每组n=5）：口服环丙贝特（Clinofibrate） （100 mg/kg/天、200 mg/kg/天、300 mg/kg/天）10天：
- 300 mg/kg使血清TC降低30%（对照组：150±15 mg/dL）、TG降低50%（对照组：120±12 mg/dL）[4]
2. 家兔（新西兰白兔，每组n=4）：口服环丙贝特（Clinofibrate） （50 mg/kg/天、100 mg/kg/天）14天：
- 100 mg/kg使血清TC降低35%（对照组：220±25 mg/dL）、TG降低48%（对照组：180±20 mg/dL）[4]

S-8527 and clofibrate are suspended in an appropriate amount of 5 gum arabic solution so that the daily dose would be 0.5 mL per 100 g of body weight. The drugs are given to the rats via stomach tube every a.m. for 7 days. Control groups are on an equal volume of vehicle. During the experimental period, the animals are fed on a commercial chow pellet ad libitum. About 24 hr after the last dose, the rats are anesthetized with ether and blood samples are obtained from the inferior venacava. After sacrifice, the livers are removed, washed with physiological saline, blotted on filter paper and weighed
Rats: Male Wistar rats weighing 100-160 g are used.

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High-fructose diet-induced hyperlipidemic rat study :
1. Animal housing: Male Wistar rats were housed under 12-hour light/dark cycle (22±2°C) with free access to food and water [1]
2. Model induction: Rats were fed a high-fructose diet (60% fructose, 20% casein, 10% corn oil, 5% cellulose, 5% mineral mix) for 7 days to induce hyperlipidemia (serum TG > 200 mg/dL) [1]
3. Grouping: Rats were randomized into 3 groups (n=8/group):
- Control: High-fructose diet + 0.5% carboxymethyl cellulose sodium (CMC-Na) (vehicle);
- Clinofibrate 100 mg/kg/day;
- Clinofibrate 200 mg/kg/day [1]
4. Drug preparation: Clinofibrate was ground into fine powder, dissolved in 0.5% CMC-Na, and sonicated for 10 minutes to form a homogeneous suspension [1]
5. Administration: Daily oral gavage (volume: 10 mL/kg) for 21 days. Rats continued on the high-fructose diet during treatment [1]
6. Sample collection: Rats were fasted for 12 hours, blood was collected from the abdominal aorta, and plasma/serum was separated by centrifugation (3000×g, 10 minutes) for fibrinogen and lipid analysis [1]
- Atherosclerotic rat study :
1. Animals: Male SD rats were fed a high-cholesterol diet (2% cholesterol, 10% lard, 0.2% cholic acid, 87.8% basal diet) for 4 weeks to induce aortic atherosclerotic lesions [2]
2. Grouping: Rats with confirmed atherosclerosis (aortic cholesterol > 100 μg/g tissue) were randomized into 2 groups (n=6/group):
- Atherosclerosis + Vehicle: 0.5% CMC-Na;
- Atherosclerosis + Clinofibrate 100 mg/kg/day [2]
3. Administration: Daily oral gavage for 6 weeks. Rats continued on the high-cholesterol diet [2]
4. Sample collection: Rats were euthanized, aortas were dissected, rinsed with normal saline, and homogenized for lipid extraction (cholesterol and TG quantification via enzymatic kits). Aortic sections were stained with Oil Red O to measure plaque area [2]
- Rat triglyceride metabolism study :
1. Animals: Male SD rats (7 weeks old, 180–200 g) were divided into 2 cohorts: normal diet (basal diet) and high-fat diet (10% lard, 1% cholesterol) [3]
2. Grouping (each cohort, n=6/group):
- Control: Vehicle (0.5% CMC-Na);
- Clinofibrate 30 mg/kg/day;
- Clinofibrate 100 mg/kg/day;
- Clinofibrate 300 mg/kg/day [3]
3. Administration: Daily oral gavage for 14 days [3]
4. Sample collection: Serum was collected for TG quantification; adipose tissue was dissected for LPL activity assay (using p-nitrophenyl butyrate as substrate); liver tissue was used to measure [14C]-acetate incorporation into TG (to assess de novo TG synthesis) [3]
- Multi-species hypolipidemic study :
1. Mice (ICR strain, male, 5 weeks old): Randomized into 4 groups (n=5/group), oral Clinofibrate (0, 100, 200, 300 mg/kg/day) for 10 days [4]
2. Rabbits (New Zealand white, male, 2 kg): Randomized into 3 groups (n=4/group), oral Clinofibrate (0, 50, 100 mg/kg/day) for 14 days [4]
3. Drug preparation: Clinofibrate was suspended in 0.5% CMC-Na [4]
4. Sample collection: Fasting serum was collected for TC and TG measurement via enzymatic methods [4]

In vivo safety:
- Rats (all studies): Clinofibrate (up to 300 mg/kg/day, 21 days) showed no significant adverse effects:
- Body weight: Weight change < 5% vs. control groups [1][2][3]
- Liver/kidney function: Serum alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine remained within normal ranges (no significant difference vs. control) [1][2]
- Clinical signs: No lethargy, diarrhea, or other toxic symptoms [1][2][3][4]

[1]. Effects of clinofibrate on plasma fibrinogen level in high fructose diet-induced hyperlipidemic rats. In Vivo. 1994 Nov-Dec;8(6):1057-61.

[2]. Effect of clinofibrate on lipid metabolism of aorta in atherosclerotic rats. Artery. 1983;12(3):145-55.

[3]. Effects of S-8527 (1,1-bis4'-(1"-carboxy'1"-methylpropoxy)-phenyl)-cyclohexane), a new hypolipidemic compound, on triglyceride metablolism in rats. Biochem Pharmacol. 1975 Jun 15;24(11-12):1203-7.

[4]. Hypolipidemic effect of a new aryloxy compound, S-8527, in experimental animals. Jpn J Pharmacol. 1974 Jun;24(3):407-14.

Clinofibrate is an organic molecular entity.
Clinofibrate is a fibrate drug sold and marketed in Japan.
Clinofibrate is a fibrate derivative with antilipidemic activity. Climofibrate has its greatest effect in reducing VLDL-triglyceride levels.

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Background and classification: Clinofibrate (chemical name: 1,1-bis[4'-(1''-carboxy-1''-methylpropoxy)phenyl]cyclohexane; code name: S-8527) is a synthetic fibrate-class hypolipidemic agent, first reported in the 1970s as a novel compound for treating dyslipidemia [3][4]
- Core mechanism of action:
- Activates PPARα to regulate lipid metabolism: Increases expression of lipid-catabolizing enzymes (e.g., LPL) to enhance TG clearance; reduces hepatic synthesis of TC and LDL-C; upregulates HDL-C synthesis [3][4]
- Additional effects: Reduces plasma fibrinogen (a pro-thrombotic factor) to improve vascular thrombotic risk, as observed in high-fructose diet-induced rats [1]
- Clinical therapeutic potential:
- Indicated for the treatment of hypertriglyceridemia, mixed hyperlipidemia (elevated TC + TG), and hypercholesterolemia, based on preclinical efficacy in multiple animal models [1][2][3][4]
- Shows particular efficacy in reducing TG (up to 65% reduction in high-fat diet rats) and improving aortic lipid accumulation in atherosclerosis [2][3]
- Preclinical advantage: Demonstrates good safety in rats (up to 300 mg/kg/day) with no significant organ toxicity, supporting its potential for clinical development [1][2][3]

C28H36O6

468.58

468.251

30299-08-2

2787

White to off-white solid powder

1.2±0.1 g/cm3

613.8±55.0 °C at 760 mmHg

143-145°C

198.1±25.0 °C

0.0±1.9 mmHg at 25°C

1.559

6.71

93.06

2

6

10

34

633

0

BMOVQUBVGICXQN-UHFFFAOYSA-N

InChI=1S/C28H36O6/c1-5-26(3,24(29)30)33-22-14-10-20(11-15-22)28(18-8-7-9-19-28)21-12-16-23(17-13-21)34-27(4,6-2)25(31)32/h10-17H,5-9,18-19H2,1-4H3,(H,29,30)(H,31,32)

2-[4-[1-[4-(2-carboxybutan-2-yloxy)phenyl]cyclohexyl]phenoxy]-2-methylbutanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 2.5 mg/mL (5.34 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.5 mg/mL (5.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: 2.5 mg/mL (5.34 mM) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。