SODIUM CLOFIBRATE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H10ClO3.Na
Molecular Weight	236.627
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CC(C)(OC1=CC=C(Cl)C=C1)C([O-])=O

InChI

InChIKey=MAUQVQSXTOZPSX-UHFFFAOYSA-M

InChI=1S/C10H11ClO3.Na/c1-10(2,9(12)13)14-8-5-3-7(11)4-6-8;/h3-6H,1-2H3,(H,12,13);/q;+1/p-1

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
Dose-dependent induction of carcinomas and glutathione S-transferase placental form negative eosinophilic foci in the rat liver by di(2-ethylhexyl)phthalate after diethylnitrosamine initiation.	1999 Aug	10478332
Structure, evolution, and liver-specific expression of sterol 12alpha-hydroxylase P450 (CYP8B).	1999 Jul	10393316
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
Mitochondrial damage by the "pro-oxidant" peroxisomal proliferator clofibrate.	1999 Nov	10569642
The relationship between decrease in Cx32 and induction of P450 isozymes in the early phase of clofibrate hepatocarcinogenesis in the rat.	1999 Sep	10550479
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
[A 50-year history of new drugs in Japan: the developments and trends of antihyperlipidemic drugs].	2001	11968219
The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.	2001	11695550
Use of real-time gene-specific polymerase chain reaction to measure RNA expression of three family members of rat cytochrome P450 4A.	2001	11424223
Cytochrome P450 1A1 and 4A activities in isolated rat spleen lymphocytes.	2001 Apr	11338675
PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator.	2001 Aug	11459802
The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor alpha is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver.	2001 Jan 5	11022051
Hormonal regulation of multiple promoters of the rat mitochondrial glycerol-3-phosphate dehydrogenase gene: identification of a complex hormone-response element in the ubiquitous promoter B.	2001 Jul	11454004
Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease.	2001 Jul	11422732
The biochemistry of hypo- and hyperlipidemic fatty acid derivatives: metabolism and metabolic effects.	2001 Jul	11412891
Accumulation of medium chain acyl-CoAs during beta-oxidation of long chain fatty acid by isolated peroxisomes from rat liver.	2001 Jun	11411544
Three-dimensional high voltage electron microscopy of thick biological specimens.	2001 Jun	11070359
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
Cytochrome p450-dependent metabolism of trichloroethylene in rat kidney.	2001 Mar	11222868
Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes.	2001 May	11356172
A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible.	2001 Nov 15	11697852
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
Peroxisome proliferator-activated receptor ligands as antiatherogenic agents: panacea or another Pandora's box?	2002 Jan	12000972
Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models.	2002 Jan	11851881
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Blunted induction of hepatic CYP4A in TNF (p55-/-/p75-/-) double receptor knockout mice following clofibrate treatment.	2002 May	12069177
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

SODIUM CLOFIBRATE

Common Name

English

PROPANOIC ACID, 2-(4-CHLOROPHENOXY)-2-METHYL-, SODIUM SALT (1:1)

Common Name

English

CLOFIBRIC ACID SODIUM SALT

Common Name

English

Code System Code Type Description

FDA UNII

G05RA8J89U