Clinofibrate

Names

[ Name ]:
Clinofibrate

[Synonym ]:
UNII:0374EZJ8CU
2-[4-[1-[4-(2-carboxybutan-2-yloxy)phenyl]cyclohexyl]phenoxy]-2-methylbutanoic acid
2,2'-[1,1-Cyclohexanediylbis(4,1-phenyleneoxy)]bis(2-methylbutanoic acid)
2,2'-[cyclohexane-1,1-diylbis(benzene-4,1-diyloxy)]bis(2-methylbutanoic acid)
Butanoic acid, 2,2'-[cyclohexylidenebis(4,1-phenyleneoxy)]bis[2-methyl-
2,2'-[Cyclohexane-1,1-diylbis(4,1-phenyleneoxy)]bis(2-methylbutanoic acid)
MFCD00865769

Biological Activity

[Description]:

Clinofibrate (S-8527) is a hypelipidemic agent and a HMG-CoA reductase inhibitor.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> HMG-CoA Reductase (HMGCR)

Research Areas >> Metabolic Disease

[In Vivo]

Clinofibrate administration (50 and 100 mg/kg/day, p.o.) significantly inhibits the increase in plasma fibrinogen level as well as serum- and VLDL-LDL-lipids[1]. Clinofibrate significantly decreases the high plasma cholesterol level of atherosclerotic rats, which is 823±256 mg/dl, or about ten times that of control rats (85±11 mg/dl). On treatment with clinofibrate, the cholesterol level is reduced most in the very low density lipoprotein (VLDL) fraction[2]. In rats which are refed either a fat-free diet or a 5% fat diet after a 2-day fast. clinofibrate at 30 mg/kg results in reductions of serum and liver triglyceride levels[3]. Oral ingestion of S-8527 to normal rats for 7 days lowers serum triglycerides and cholesterol by about 27% at 1 mg/kg and 20% at 3 mg/kg, respectively. S-8527 at 3 mg/kg decreases liver triglyceride concentration by about 20%[4].

[Animal admin]

Rats: Male Wistar rats weighing 100-160 g are used. 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[4].

[References]

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

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

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

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
613.8±55.0 °C at 760 mmHg

[ Melting Point ]:
143-145°C

[ Molecular Formula ]:
C₂₈H₃₆O₆

[ Molecular Weight ]:
468.582

[ Flash Point ]:
198.1±25.0 °C

[ Exact Mass ]:
468.251190

[ PSA ]:
93.06000

[ LogP ]:
6.71

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.559

[ Storage condition ]:
Refrigerator

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: ES8900000

CHEMICAL NAME :: Butyric acid, 2,2'-cyclohexane-1,1-diylbis(p-phenyleneoxy)bis-(2-me thyl-

CAS REGISTRY NUMBER :: 30299-08-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C28-H36-O6

MOLECULAR WEIGHT :: 468.64

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,219,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 205 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 12,933,1981

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1930 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,219,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >150 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,219,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1600 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,219,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 230 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair

REFERENCE :: YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 23,1553,1981

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 350 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,219,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 150 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 12,933,1981

Related Compounds

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