CAS 49562-28-9|Fenofibrate

Introduction：Basic information about CAS 49562-28-9|Fenofibrate, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Fenofibrate BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Articles129
8. Synonyms

Common Name	Fenofibrate
CAS Number	49562-28-9	Molecular Weight	360.831
Density	1.2±0.1 g/cm3	Boiling Point	469.8±35.0 °C at 760 mmHg
Molecular Formula	C₂₀H₂₁ClO₄	Melting Point	80-81ºC
MSDS	ChineseUSA	Flash Point	165.4±24.9 °C

Names

Name	fenofibrate
Synonym	More Synonyms

Fenofibrate BiologicalActivity

Description	Fenofibrate is a PPARα agonist with an EC50 of 30 μM.
Related Catalog	Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Metabolic Enzyme/Protease >>Cytochrome P450Signaling Pathways >>Cell Cycle/DNA Damage >>PPARResearch Areas >>Cardiovascular Disease
Target	CYP2C19:0.2 μM (IC50) CYP2B6:0.7 μM (IC50) CYP2C9:9.7 μM (IC50) CYP2C8:4.8 μM (IC50) CYP3A4:142.1 μM (IC50) PPARα:30 μM (IC50)
In Vitro	Fenofibrate is a relatively potent inhibitor of CYP2B6 (IC50=0.7±0.2 μM) and CYP2C19 (IC50=0.2±0.1 μM). Fenofibrate is also a moderate inhibitor of CYP2C8 (IC50=4.8±1.7 μM) and CYP2C9 (IC50=9.7 μM)[1]. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. Fenofibrate is a well-known PPARα agonist, but an in vitro assessment of 209 frequently prescribed drugs and related xenobiotics suggests that Fenofibrate is also a potent inhibitor of cytochrome P450 epoxygenase (CYP)2C. The affinity of Fenofibrate to CYP2C is >10 times higher (EC50=2.39±0.4 μM) than to PPARα (EC50=30 μM). Fenofibrate at a low dose inhibits CYP2C8 activity without PPARα activation[2].
In Vivo	Daily intake of Fenofibrate at this low dose (10 μg/g/day) inhibits retinal and choroidal neovascularization induced by CYP2C8 overexpression by 29% (P=0.021) and 36% (P=1.2×10−9) respectively[2].
Kinase Assay	The half-maximal inhibitory concentrations (IC50s) of Fenofibrate, statins (atorvastatin, lovastatin, pravastatin, simvastatin and simvastatin acid, the active form of simvastatin) and glipizide for recombinant human CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 are determined using fluorometric CYP450 inhibition assays. Briefly, the drugs are dissolved in methanol or acetonitrile. In 96 well assay plates, the drugs are diluted to a series of concentrations in a solution containing cofactors including NADP+ (final concentration 1.3 mM), MgCl2 (final concentration 3.3 m M), glucose-6-phosphate (G6P, final concentration 3.3 mM) and glucose 6-phosphate dehydrogenase (final concentration 0.4 U/mL). The mixture is pre-incubated at 37°C for 10 min. The enzymes and fluorogenic substrates are diluted to desired concentrations in sodium phosphate reaction buffer (pH 7.4, final concentration 200 mM) and mixed. Reactions are initiated with addition of the enzyme and substrate mixture to the cofactor and drug mixture. The final reaction volume of all assays is 200 μL. After incubating at 37°C for a pre-specified period of time (15 to 45 min), the reactions are stopped with addition of 75 μL quenching solution (0.5 M Tris base or 2N NaOH). Fluorescence is determined using a BioTek Synergy 2 fluorescence reader. Each of the drugs is tested at eight concentrations in duplicate. To estimate IC50s, percent of inhibition is calculated using net fluorescence that is corrected for the background. The values of percent of inhibition are then fitted to a three or four parameter log-logistic model[1].
Animal Admin	Mice[2] The mouse oxygen-induced retinopathy (OIR) model is used. Briefly to induce retinal neovascularization, mouse pups and their nursing mother are exposed to 75±3% oxygen from P7 to P12. For the higher dose Fenofibrate (F6020) treatment (100 mg/kg/day). Fenofibrate is dissolved in corn oil to make 100mg/mL solution and pure corn oil is used as vehicle control. For the lower dose treatment (10 mg/kg/day), Fenofibrate is dissolved in 10% DMSO, D2650 to make a 10 mg/mL solution and 10% DMSO is used as vehicle control. After return to room air, mice are orally gavaged with Fenofibrate (100 or 10 mg/kg) or vehicle control daily from P12 to P16. At P17, eyes are enucleated immediately after euthanasia and fixed in 4% paraformaldehyde in PBS for 1 h at room temperature. Retinas are then dissected and stained overnight with Alexa Fluor 594 conjugated isolectin GS-IB4 (10 μg/mL) at room temperature. After washing with PBS, retinas are mounted onto microscope slides with photoreceptor side down and embedded in SlowFade antifade mounting medium. Retinal images are taken using a fluorescence microscope with image software. Retinal neovascularization is analyzed.
References	[1]. Schelleman H, et al. Pharmacoepidemiologic and in vitro evaluation of potential drug-drug interactions of sulfonylureas with fibrates and statins. Br J Clin Pharmacol. 2014 Sep;78(3):639-48. [2]. Gong Y, et al. Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis. EBioMedicine. 2016 Sep 30. pii: S2352-3964(16)30448-0.

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	469.8±35.0 °C at 760 mmHg
Melting Point	80-81ºC
Molecular Formula	C₂₀H₂₁ClO₄
Molecular Weight	360.831
Flash Point	165.4±24.9 °C
Exact Mass	360.112823
PSA	52.60000
LogP	4.80
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.547
InChIKey	YMTINGFKWWXKFG-UHFFFAOYSA-N
SMILES	CC(C)OC(=O)C(C)(C)Oc1ccc(C(=O)c2ccc(Cl)cc2)cc1
Storage condition	Store at RT
Water Solubility	Practically insoluble in water, very soluble in methylene chloride, slightly soluble in ethanol (96 per cent)

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UA2453400

CHEMICAL NAME :: Propanoic acid, 2-(4-(4-chlorobenzoyl)phenoxy)-2-methyl-, 1-methylethyl ester

CAS REGISTRY NUMBER :: 49562-28-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 14

MOLECULAR FORMULA :: C20-H21-Cl-O4

MOLECULAR WEIGHT :: 360.86

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 :: >2 gm/kg

TOXIC EFFECTS :: Liver - other changes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S873,1995

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 :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,885,1976

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >4 gm/kg

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

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S873,1995

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: >5 gm/kg

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

REFERENCE :: AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 83(Suppl 5B),26,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2730 mg/kg/13W-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - normocytic anemia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S881,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 9100 mg/kg/52W-I

TOXIC EFFECTS :: Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S903,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 81900 mg/kg/13W-I

TOXIC EFFECTS :: Blood - normocytic anemia Blood - changes in platelet count Related to Chronic Data - death

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S923,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 36400 mg/kg/52W-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - normocytic anemia

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S949,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 84 gm/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male Reproductive - Maternal Effects - other effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S973,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 22 gm/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - behavioral

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S983,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1100 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S983,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 26 gm/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S1001,1995

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5855 mg/kg

SEX/DURATION :: female 7-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987- Volume(issue)/page/year: 64,286,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 117 mg/kg

SEX/DURATION :: female 7-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987- Volume(issue)/page/year: 64,286,1989

Safety Information

Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes	Xn:Harmful
Risk Phrases	R22
Safety Phrases	S36
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	UA2453400
HS Code	2932999099

Customs

HS Code	2932999099
Summary	2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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Synonyms

propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate

Lipantil

Isopropyl 2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropionate

Procetofen

2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropionic Acid Isopropyl Ester

Fenofibrate

Lipidil

Tricor

Isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate

2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid isopropyl ester

Lipanthyl

Supralip

Secalip

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