BEZAFIBRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20ClNO4
Molecular Weight	361.819
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(OC1=CC=C(CCNC(=O)C2=CC=C(Cl)C=C2)C=C1)C(O)=O

InChI

InChIKey=IIBYAHWJQTYFKB-UHFFFAOYSA-N

InChI=1S/C19H20ClNO4/c1-19(2,18(23)24)25-16-9-3-13(4-10-16)11-12-21-17(22)14-5-7-15(20)8-6-14/h3-10H,11-12H2,1-2H3,(H,21,22)(H,23,24)

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Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16168052
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9171241 | https://www.ncbi.nlm.nih.gov/pubmed/24759758

Bezafibrate is a lipid-lowering fibric acid derivative. Bezafibrate directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2678	37.37 µM [EC50]
Peroxisome proliferator-activated receptor delta 29 Target ID: CHEMBL3979 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2678	40.3 µM [EC50]
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2678	64.76 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperlipidemia 80 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3301301 https://www.ncbi.nlm.nih.gov/pubmed/18629356	Primary		Approved 8429	BEZALIP Approved Use Bezafibrate belongs to a group of medicines known as lipid-lowering substances.

PubMed

Title	Date	PubMed
Uncoupling protein-3 mRNA levels are increased in white adipose tissue and skeletal muscle of bezafibrate-treated rats.	1999 Jul 5	10403804
Combined effects of probucol and benzafibrate on lipoprotein metabolism and liver cholesteryl ester transfer protein mRNA in cholesterol-fed rabbits.	1999 Jun	10406588
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.	1999 Jun	10364093
Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment.	2000 Apr	10780315
Peroxisome proliferator-activated receptor alpha (PPARalpha) activators, bezafibrate and Wy-14,643, increase uncoupling protein-3 mRNA levels without modifying the mitochondrial membrane potential in primary culture of rat preadipocytes.	2000 Aug 15	10933891
The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia is mediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding.	2000 Dec	11164425
Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent?	2000 Dec	11096145
Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene.	2000 Jul	10909982
Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease.	2000 Jul 4	10880410
Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment.	2000 Mar 1	10716467
A paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate.	2000 Oct	11064678
Antihypertensive mechanisms of lipid-lowering drugs: decoding the Rosetta stone's inscriptions'.	2001 Apr	11330868
Differential involvement of peroxisome-proliferator-activated receptors alpha and delta in fibrate and fatty-acid-mediated inductions of the gene encoding liver fatty-acid-binding protein in the liver and the small intestine.	2001 Apr 15	11284737
Rhabdomyolysis and acute renal failure following a switchover of therapy between two fibric acid derivatives.	2001 Aug	11764054
Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S.	2001 Dec 18	11748098
Bezafibrate induces acyl-CoA oxidase mRNA levels and fatty acid peroxisomal beta-oxidation in rat white adipose tissue.	2001 Jan	11216866
The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells.	2001 Jan	11172467
The role of fibric acids in atherosclerosis.	2001 Jan	11123853
Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease.	2001 Jul	11422732
Treating dyslipidaemia in non-insulin-dependent diabetes mellitus -- a special reference to statins.	2001 Jul-Aug	11457674
Long-term diuretic therapy in patients with coronary disease: increased colon cancer-related mortality over a 5-year follow-up.	2001 Jun	11439311
Effect of bezafibrate in primary biliary cirrhosis: a pilot study.	2001 Jun	11422787
Three-dimensional high voltage electron microscopy of thick biological specimens.	2001 Jun	11070359
Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.	2001 Mar	11579993
Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.	2001 Mar	11519881
[Drug interactions of lipid-lowering drugs and precaution of clinical use].	2001 Mar	11347155
[Overviews of fibrate].	2001 Mar	11347141
[Drug combination therapies for patients with hyperlipidemia and its significance].	2001 Mar	11347133
[BECAIT [Bezafibrate Coronary Atherosclerosis Intervention Trial]].	2001 Mar	11347109
Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention?	2001 Nov	11684067
Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats.	2001 Nov	11679425
Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism.	2001 Nov 23	11730728
Variation at position 162 of peroxisome proliferator-activated receptor alpha does not influence the effect of fibrates on cholesterol or triacylglycerol concentrations in hyperlipidaemic subjects.	2001 Oct	11668221
Soluble intercellular adhesion molecule-1 and long-term risk of acute coronary events in patients with chronic coronary heart disease. Data from the Bezafibrate Infarction Prevention (BIP) Study.	2002 Apr 3	11923036
[A case of primary sclerosing cholangitis presenting transient hypoperfusion and treated with bezafibrate beneficially].	2002 Feb	11877955
Investigation into the efficacy of bezafibrate against primary biliary cirrhosis, with histological references from cases receiving long term monotherapy.	2002 Jan	11808959
Severity of angina pectoris and risk of ischemic stroke.	2002 Jan	11779917
Evaluation of myopathy risk for HMG-CoA reductase inhibitors by urethane infusion method.	2002 Mar	11913531
Are high-density lipoprotein and triglyceride levels important in secondary prevention: impressions from the BIP and VA-HIT trials.	2002 Mar	11911905

Patents

Sample Use Guides

In Vivo Use Guide

Bezafibrate recommended dosage is 200 mg 3 times daily, or alternatively 400 mg once daily as a sustained-release preparation.

Route of Administration: Oral

In Vitro Use Guide

400 uM bezafibrate increases in the levels of carnitine palmitoyltransferase II activity, mitochondrial fatty acid β-oxidation, intracellular ATP, and mitochondrial membrane potential in human fibroblasts

Name

Type

Language

BEZAFIBRATE

Official Name

English

BM 15.075

Code

English

2-(P-(2-(P-CHLOROBENZAMIDO)ETHYL)PHENOXY)-2-METHYLPROPIONIC ACID

Common Name

English

BEZAFIBRATE [JAN]

Common Name

English

BEZAFIBRATE [USAN]

Common Name

English

BEZAFIBRATE [EP MONOGRAPH]

Common Name

English

Bezafibrate [WHO-DD]

Common Name

English

bezafibrate [INN]

Common Name

English

PROPANOIC ACID, 2-(4-(2-((4-CHLOROBENZOYL)AMINO)ETHYL)PHENOXY)-2-METHYL-

Common Name

English

BM-15075

Code

English

BM-15.075

Code

English

NSC-758174

Code

English

BEZATOL SR

Brand Name

English

BEZAFIBRATE [MI]

Common Name

English

BEZAFIBRATE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC10AB02