FENOFIBRIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H15ClO4
Molecular Weight	318.752
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=MQOBSOSZFYZQOK-UHFFFAOYSA-N

InChI=1S/C17H15ClO4/c1-17(2,16(20)21)22-14-9-5-12(6-10-14)15(19)11-3-7-13(18)8-4-11/h3-10H,1-2H3,(H,20,21)

HIDE SMILES / InChI

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17343371	Agonist 2752		4500.0 nM [EC50]
Fatty acid binding protein intestinal 2 Target ID: CHEMBL4879 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18533710	Inhibitor 8504		1000.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
hypertriglyceridemia 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022418s011lbl.pdf	Primary		Approved 8583	FIBRICOR Approved Use FIBRICOR is a peroxisome proliferator receptor alpha (PPARα) activator indicated as an adjunct to diet: to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia (> 500 mg/dL); to reduce elevated total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), TG and apolipoprotein (Apo) B and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. Launch Date 2009

C_max

Value	Dose	Co-administered	Analyte	Population
12 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf	105 mg 1 times / day single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOFIBRIC ACID plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FASTED
8.37 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf	105 mg 1 times / day single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOFIBRIC ACID plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
162.96 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf	105 mg 1 times / day single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOFIBRIC ACID plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FASTED
124.89 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf	105 mg 1 times / day single, oral dose: 105 mg route of administration: Oral experiment type: SINGLE co-administered:		FENOFIBRIC ACID plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf	105 mg 1 times / day steady-state, oral dose: 105 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		FENOFIBRIC ACID serum	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
135 mg 1 times / day multiple, oral Recommended Dose: 135 mg, 1 times / day Route: oral Route: multiple Dose: 135 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022224s003lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022224s003lbl.pdf	Other AEs: Constipation, Diarrhea... Other AEs: Constipation (3.3%) Diarrhea (3.9%) Dyspepsia (3.7%) Nausea (4.3%) Fatigue (2%) Pain (3.5%) Nasopharyngitis (3.5%) Sinusitis (3.3%) Upper respiratory tract infection (5.3%) ALT increased (1.2%) Arthralgia (3.9%) Back pain (6.3%) Muscle spasms (1.6%) Myalgia (3.3%) Pain in extremity (4.5%) Dizziness (4.1%) Headache (12.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022224s003lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087 inhibitor 2252	substrate 1193 inducer 440 inhibitor 2438	substrate 1388 inducer 109 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 926 CYP2C8 1057 CYP2E1 1060 CYP1A2 2153 P-gp 1741 OATP1B1 1079 CYP2C19 2057 CYP2A6 879 OAT3 747	CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 CYP2E1 729 UGT1A3 470 UGT1A6 343 UGT1A9 423 UGT2B7 456	CYP1A2 832 CYP2A6 86 CYP2B6 669 CYP2C19 329 CYP2E1 131 CYP2C8 198 UGT1A1 78

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021350s005lbl.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922314/	moderate
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=7 Page: 7.0	no
CYP2A6 911	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=7 Page: 7.0	no
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=7 Page: 7.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=7 Page: 7.0	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/14698041/	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021350s005lbl.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922314/	weak
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021350s005lbl.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922314/	weak
UGT1A1 303	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/15771232/	weak
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17314201/	yes [IC50 2.2 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16316932/	yes [IC50 20 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	yes [IC50 282 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0	yes [IC50 741 uM]	weak (co-administration study) Comment: IC50 value from pre-incubation study; Coadministration with efavirenz (CYP2B6 substrate) resulted in AUC decrease of efavirenz by 12% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022418s000_ClinPharmR.pdf#page=11 Page: 11.0

Drug as victim

Target	Modality	Activity
UGT2B7 456	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774983/	major
UGT1A3 470	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774983/	minor
UGT1A6 343	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774983/	minor
UGT1A9 423	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774983/	minor
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022418lbl.pdf#page=6 Page: 6.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:83469	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:83469
ChemicalBook	CB8400259	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8400259
eMolecules	591140	https://www.emolecules.com/cgi-bin/more?vid=591140
MolPort	MolPort-000-002-475	https://www.molport.com/shop/molecule-link/MolPort-000-002-475
ZINC	ZINC000000001984	http://zinc15.docking.org/substances/ZINC000000001984

PubMed

Title	Date	PubMed
Drug treatment of combined hyperlipidemia.	2001	14728015
Micronized fenofibrate in dyslipidemia: a focus on plasma high-density lipoprotein cholesterol (HDL-C) levels.	2002	14727988
Randomised crossover studies of the bioequivalence of two fenofibrate formulations after administration of a single oral dose in healthy volunteers.	2002	11963648
Fenofibrate in the treatment of dyslipidemia: a review of the data as they relate to the new suprabioavailable tablet formulation.	2002 Dec	12581543
A laser flash photolysis study of fenofibric acid in aqueous buffered media: unexpected triplet state inversion in a derivative of 4-alkoxybenzophenone.	2002 Mar	11950084
Induction of plasminogen activator inhibitor-1 in endothelial cells by basic fibroblast growth factor and its modulation by fibric acid.	2002 May 1	12006402
Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins.	2003 Apr	12644596
Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells.	2003 Aug 15	12954370
Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme.	2003 Aug 29	12810707
An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers.	2003 Feb	12749507
A chemical switch regulates fibrate specificity for peroxisome proliferator-activated receptor alpha (PPARalpha ) versus liver X receptor.	2003 Jan 24	12441342
Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists.	2003 Jun	12790802
Influence of lipid lowering fibrates on P-glycoprotein activity in vitro.	2004 Jan 15	14698041
Fenofibrate and fenofibric acid analysis by capillary electrophoresis.	2004 Jun	15188253
A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice.	2004 Jun	14982965
Cardiovascular drugs inhibit MMP-9 activity from human THP-1 macrophages.	2004 May	15169608
Optimal lipid modification: the rationale for combination therapy.	2005	17315604
Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner.	2005 Jun	15790930
Fenofibrate: a novel formulation (Triglide) in the treatment of lipid disorders: a review.	2006	17722529
The effects of food on the bioavailability of fenofibrate administered orally in healthy volunteers via sustained-release capsule.	2006	16584288
Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation.	2006 Feb	16502765
Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro.	2006 Nov 24	17022944
Determination of fenofibric acid concentrations by HPLC after anion exchange solid-phase extraction from human serum.	2007 Apr	17417074
Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI.	2007 Aug	17533223
Atorvastatin glucuronidation is minimally and nonselectively inhibited by the fibrates gemfibrozil, fenofibrate, and fenofibric acid.	2007 Aug	17470524
LC-MS analysis and environmental risk of lipid regulators.	2007 Feb	17047939
Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope LbetaT2 cells.	2007 Jul	17592024
Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein.	2007 May	17314201
Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing.	2008	19183747
Statins Activate Human PPARalpha Promoter and Increase PPARalpha mRNA Expression and Activation in HepG2 Cells.	2008	19125197
Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin/kexin type 9.	2008 Apr 11	18245819
A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet.	2008 May	18212024
Treatment of hyperlipidaemia with fenofibrate and related fibrates.	2008 Oct	18808320
Fenofibric acid: in combination therapy in the treatment of mixed dyslipidemia.	2009	19929038
MBX-102/JNJ39659100, a novel non-TZD selective partial PPAR-γ agonist lowers triglyceride independently of PPAR-α activation.	2009	19404482
Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression.	2009 Apr	19220292
Fenofibrate-loaded PLGA microparticles: effects on ischemic stroke.	2009 Apr 11	19168134
Advances in the medical treatment of diabetic retinopathy.	2009 Aug	19638526
Peroxisome-proliferator-activated receptor-alpha activation protects brain capillary endothelial cells from oxygen-glucose deprivation-induced hyperpermeability in the blood-brain barrier.	2009 Aug	19534718
Capecitabine-induced severe hypertriglyceridaemia and diabetes: a case report and review of the literature.	2009 Dec	20002489
Efficacy and safety of ABT-335 (fenofibric acid) in combination with atorvastatin in patients with mixed dyslipidemia.	2009 Feb 15	19195513
Differentiated CaCo-2 cells as an in-vitro model to evaluate de-novo apolipoprotein A-I production in the small intestine.	2009 Jun	19445040
Fenofibrate metabolism in the cynomolgus monkey using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics.	2009 Jun	19251819
Characterization of lipophilic drug binding to rat intestinal fatty acid binding protein.	2009 Jun	19160019
Fenofibric Acid (trilipix).	2009 May 4	19417718
Myopathy with statin-fibrate combination therapy: clinical considerations.	2009 Sep	19636324
Determination of fenofibric acid in human plasma by ultra performance liquid chromatography-electrospray ionization mass spectrometry: application to a bioequivalence study.	2009 Sep	19353730
Medicinal chemistry of drugs used in diabetic cardiomyopathy.	2010	20015035
Occurrence of emerging pollutants in urban wastewater and their removal through biological treatment followed by ozonation.	2010 Jan	19628245
Ecotoxicity assessment of lipid regulators in water and biologically treated wastewater using three aquatic organisms.	2010 Jan	19333638

Name

Type

Language

FENOFIBRIC ACID

Common Name

English

FENOFIBRATE RELATED COMPOUND B

Preferred Name

English

PROCETOFENIC ACID

Common Name

English

FIBRICOR

Brand Name

English

FENOFIBRIC ACID [ORANGE BOOK]

Common Name

English

FENOFIBRATE FREE ACID [MI]

Common Name

English

FENOFIBRATE RELATED COMPOUND B [USP-RS]

Common Name

English

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

Common Name

English

LF-153

Code

English

FENOFIBRIC ACID [VANDF]

Common Name

English

NSC-281318

Code

English

FENOFIBRIC ACID [USP-RS]

Common Name

English

Fenofibric acid [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175596