CALCIUM CLOFIBRATE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C10H10ClO3.Ca
Molecular Weight	467.353
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Ca++].CC(C)(OC1=CC=C(Cl)C=C1)C([O-])=O.CC(C)(OC2=CC=C(Cl)C=C2)C([O-])=O

InChI

InChIKey=IXCILCKRXAZYGP-UHFFFAOYSA-L

InChI=1S/2C10H11ClO3.Ca/c2*1-10(2,9(12)13)14-8-5-3-7(11)4-6-8;/h2*3-6H,1-2H3,(H,12,13);/q;;+2/p-2

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7853724 | https://www.ncbi.nlm.nih.gov/pubmed/27354598

Clofibrate is a fibric acid derivative used to lower cholesterol and triglyceride (fat-like substances) levels in the blood. This may help prevent medical problems caused by such substances clogging the blood vessels. However, this treatment was discontinued in 2002 due to adverse effects. Clofibrate is an agonist of the PPAR-α receptor in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, and increased lipoprotein lipase activity. Clofibrate increased the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis, inhibited the synthesis, and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. In addition, clofibrate was investigated as a novel therapy agent in multiple myeloma and it shown the promising results.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19817384	Agonist 2752	50.0 µM [EC50]
Taste receptor type 1 member 3 14 Target ID: Q7RTX0 Gene ID: 83756.0 Gene Symbol: TAS1R3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19817384	Inhibitor 8504	28.0 µM [IC50]
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10922459	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperlipoproteinemia 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7853724	Primary		Approved 8583	ATROMID-S Approved Use Unknown Launch Date 1967
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27354598	Primary		Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
216 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7550835/	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CLOFIBRIC ACID plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
30649 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7550835/	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CLOFIBRIC ACID plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
103.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7550835/	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		CLOFIBRIC ACID plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 1079 MRP2 499 P-gp 1741		CYP4A1 17 CYP2B1 26 UGT 32

Drug as perpetrator

Target	Modality	Activity
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/ Page: 6.0	moderate [Inhibition 100 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/	no
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/	not significant
CYP2B1 41	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/7685601/	yes
CYP4A1 25	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/7685601/	yes
UGT 70	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/11033061/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:34648	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:34648
ChemicalBook	CB1282957	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1282957
eMolecules	487665	https://www.emolecules.com/cgi-bin/more?vid=487665
MolPort	MolPort-000-146-057	https://www.molport.com/shop/molecule-link/MolPort-000-146-057
ZINC	ZINC000000001187	http://zinc15.docking.org/substances/ZINC000000001187

PubMed

Title	Date	PubMed
Effects of clofibrate in primary biliary cirrhosis hypercholesterolemia and gallstones.	1975 Oct	1175893
Acyl-CoA thioesterases belong to a novel gene family of peroxisome proliferator-regulated enzymes involved in lipid metabolism.	2000	11330065
[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs].	2001	11968219
Use of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation.	2001	11764926
How well tolerated are lipid-lowering drugs?	2001	11599634
Effect of bezafibrate and clofibrate on the heme-iron geometry of ferrous nitrosylated heme-human serum albumin: an EPR study.	2001 Apr	11374593
WY-14,643 and other agonists of the peroxisome proliferator-activated receptor reveal a new mode of action for salicylic acid in soybean disease resistance.	2001 Apr	11346966
Cytochrome P450 1A1 and 4A activities in isolated rat spleen lymphocytes.	2001 Apr	11338675
Stimulatory effect of clofibrate on the action of estradiol in the mammary gland but not in the uterus of rats.	2001 Apr	11259527
Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays.	2001 Apr 27	11328961
Peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.	2001 Dec	11871124
The use of fibrates and of statins in preventing atherosclerosis in diabetes.	2001 Dec	11801860
Detection of DNA adducts using a quantitative long PCR technique and the fluorogenic 5' nuclease assay (TaqMan).	2001 Dec 12	11733068
Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat.	2001 Feb	11269691
Long-chain fatty acids regulate liver carnitine palmitoyltransferase I gene (L-CPT I) expression through a peroxisome-proliferator-activated receptor alpha (PPARalpha)-independent pathway.	2001 Feb 15	11171094
The biochemistry of hypo- and hyperlipidemic fatty acid derivatives: metabolism and metabolic effects.	2001 Jul	11412891
Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones.	2001 Jul 6	11319222
Accumulation of medium chain acyl-CoAs during beta-oxidation of long chain fatty acid by isolated peroxisomes from rat liver.	2001 Jun	11411544
Unique gene expression patterns in liver and kidney associated with exposure to chemical toxicants.	2001 Jun	11356909
Characterization of the promoter region of the human peroxisomal multifunctional enzyme type 2 gene.	2001 Jun 1	11374894
Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial.	2001 Jun 15	11408495
[Overviews of fibrate].	2001 Mar	11347141
Allosteric modification of oxygen delivery by hemoglobin.	2001 Mar	11226087
Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney.	2001 Mar	11222868
The expression of PPAR-associated genes is modulated through postnatal development of PPAR subtypes in the small intestine.	2001 Mar 30	11278173
Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes.	2001 May	11356172
Modulation of cytosolic phospholipase A(2) by PPAR activators in human preadipocytes.	2001 May	11352978
Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro.	2002 Apr	11918743
Role of hypolipidemic drug clofibrate in altering iron regulatory proteins IRP1 and IRP2 activities and hepatic iron metabolism in rats fed a low-iron diet.	2002 Apr 15	11969379
Effects of fatty acids on mitochondrial beta-oxidation enzyme gene expression in renal cell lines.	2002 Aug	12110517
Eighth World Congress of Intensive and Critical Care Medicine, 28 October-1 November 2001, Sydney, Australia: Harm minimization and effective risk management.	2002 Feb	11940273
Do lipid-lowering drugs cause erectile dysfunction? A systematic review.	2002 Feb	11818357
Characterization of catechol glucuronidation in rat liver.	2002 Feb	11792691
Synergistic effect of 4-hydroxynonenal and PPAR ligands in controlling human leukemic cell growth and differentiation.	2002 Feb 1	11827749
In vitro induction of bilirubin conjugation in primary rat hepatocyte culture.	2002 Feb 15	11829457
Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models.	2002 Jan	11851881
CYP1A-mediated metabolism of the Janus kinase-3 inhibitor 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline: structural basis for inactivation by regioselective O-demethylation.	2002 Jan	11744615
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.	2002 Jul	12087064
Effects of peroxisome proliferator-activated receptor agonists on LPS-induced neuronal death in mixed cortical neurons: associated with iNOS and COX-2.	2002 Jun 21	12031542
Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48.	2002 Jun 21	11925428
Potentiation of TNF-alpha-stimulated group IIA phospholipase A(2) expression by peroxisome proliferator-activated receptor alpha activators in rat mesangial cells.	2002 Mar	11856764
Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats.	2002 Mar 1	11911851
Myopathy and rhabdomyolysis with lipid-lowering drugs.	2002 Mar 10	11869826
Clofibrate-induced relocation of phosphatidylcholine transfer protein to mitochondria in endothelial cells.	2002 Mar 10	11855861
Getting a GRIP on liprins.	2002 Mar 28	11931733
Blunted induction of hepatic CYP4A in TNF (p55-/-/p75-/-) double receptor knockout mice following clofibrate treatment.	2002 May	12069177
Lipid-lowering drug use and cardiovascular events after myocardial infarction.	2002 May	11978147
Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages.	2002 May 1	11971025
Exposure simulation for pharmaceuticals in European surface waters with GREAT-ER.	2002 May 10	11988357

Patents

Sample Use Guides

In Vivo Use Guide

For oral dosage form (capsules): for high cholesterol: adults—1.5 to 2 grams a day. This is divided into two to four doses. Children—Dose must be determined by doctor.

Route of Administration: Oral

In Vitro Use Guide

The antitumor apoptotic effect of clofibrate at doses ranging from 0.1-600 μM was investigated on four human and one murine myeloma cell lines, as well as in two human lymphoma cell lines, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay. Clofibrate significantly reduced cell viability in all tested myeloma and lymphoma cell lines in a dose-dependent manner, while healthy cells were hardly affected.

Name

Type

Language

CALCIUM 2-(P-CHLOROPHENOXY)-2-METHYLPROPIONATE

Preferred Name

English

CALCIUM CLOFIBRATE

Official Name

English

CALCIUM CLOFIBRATE [MART.]

Common Name

English

calcium clofibrate [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98150