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 2678	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 8297	28.0 µM [IC50]
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10922459	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperlipoproteinemia 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7853724	Primary		Approved 8429	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 788 MRP2 383 P-gp 1461		CYP4A1 17 CYP2B1 26 UGT 29

Drug as perpetrator

Target	Modality	Activity
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/ Page: 6.0	moderate [Inhibition 100 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/	no
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/	not significant
CYP2B1 41	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/7685601/	yes
CYP4A1 25	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/7685601/	yes
UGT 59	inducer 1573 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
MolPort	MolPort-000-146-057	https://www.molport.com/shop/molecule-link/MolPort-000-146-057
ZINC	ZINC000000001187	http://zinc15.docking.org/substances/ZINC000000001187
eMolecules	487665	https://www.emolecules.com/cgi-bin/more?vid=487665

PubMed

Title	Date	PubMed
Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment.	1975 Aug	1143089
Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth.	1999 Jun	10342807
Hypophysectomy and/or peroxisome proliferators strongly influence the levels of phase II xenobiotic metabolizing enzymes in rat testis.	1999 Sep 30	10528994
The PPARs: from orphan receptors to drug discovery.	2000 Feb 24	10691680
Involvement of the peroxisome proliferator-activated receptor alpha in regulating long-chain acyl-CoA thioesterases.	2000 May	10787442
[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs].	2001	11968219
[Fibrate influence on lipids and insulin resistance in patients with metabolic syndrome].	2001	11957820
Use of isotopes and LC-MS-ESI-TOF for mechanistic studies of tienilic acid metabolic activation.	2001	11764926
Tg.AC genetically altered mouse: assay working group overview of available data.	2001	11695563
[Necrotizing myopathies].	2001	11596379
Use of real-time gene-specific polymerase chain reaction to measure RNA expression of three family members of rat cytochrome P450 4A.	2001	11424223
Effect of bezafibrate and clofibrate on the heme-iron geometry of ferrous nitrosylated heme-human serum albumin: an EPR study.	2001 Apr	11374593
Characterization of clofibrate-induced retrograde Golgi membrane movement to the endoplasmic reticulum: clofibrate distinguishes the Golgi from the trans Golgi network.	2001 Aug	11577722
Binding constant determination of drugs toward subdomain IIIA of human serum albumin by near-infrared dye-displacement capillary electrophoresis.	2001 Aug	11519955
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
The transcription of the peroxisome proliferator-activated receptor alpha gene is regulated by protein kinase C.	2001 Dec 15	11701232
Major clofibrate effects on liver and plasma lipids are independent of changes in polyunsaturated fatty acid composition induced by dietary fat.	2001 Feb	11269691
Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects.	2001 Feb	11175492
The peroxisomal proliferator clofibrate enhances the hepatic cytoplasmic movement of fatty acids in rats.	2001 Feb	11172343
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
Allosteric modification of oxygen delivery by hemoglobin.	2001 Mar	11226087
Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney.	2001 Mar	11222868
Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices.	2001 Nov	11703563
A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible.	2001 Nov 15	11697852
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
Do lipid-lowering drugs cause erectile dysfunction? A systematic review.	2002 Feb	11818357
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.	2002 Jul	12087064
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
Blunted induction of hepatic CYP4A in TNF (p55-/-/p75-/-) double receptor knockout mice following clofibrate treatment.	2002 May	12069177
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 CLOFIBRATE

Official Name

English

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

Common Name

English

CALCIUM CLOFIBRATE [MART.]

Common Name

English

calcium clofibrate [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98150