Identification

Name
Fenofibric acid
Accession Number
DB13873
Type
Small Molecule
Groups
Approved
Description

Fenofibrate is a third generation fibric acid derivative that is predominantly administered as monotherapy to decrease elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, apolipoprotein B and alternatively to increase high-density lipoprotein cholesterol in patients diagnosed with primary hyperlipidemia or mixed dyslipidemia and to reduce triglycerides in patients with severe hypertriglyceridemia [Label]. Fenofibrate however is generally extremely lipophilic, largely insoluble in water, and poorly absorbed [1]. As the primary active metabolite of fenofibrate however, various hydrophilic salt formulations of fenofibric acid have since been developed, resulting in therapeutic agents that demonstrate far greater solubility, absorption throughout the gastrointestinal tract, bioavailability, and capability to be administered irrespective of patient food intake [Label].

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Choline fenofibrate4BMH7IZT98856676-23-8JWAZHODZSADEHB-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fenofibric AcidCapsule, delayed release45 mg/1OralImpax Generics2016-09-12Not applicableUs
Fenofibric AcidCapsule, delayed release45 mg/1OralImpax Generics2008-12-15Not applicableUs
Fenofibric AcidTablet105 mg/1OralHalton Laboratories2015-07-30Not applicableUs
Fenofibric AcidTablet35 mg/1OralHalton Laboratories2015-07-30Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralImpax Generics2016-09-12Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralImpax Generics2008-12-15Not applicableUs00115 1460 10 nlmimage10 37459bdc
FibricorTablet105 mg/1OralAralez Pharmaceuticals Us Inc.2017-08-05Not applicableUs
FibricorTablet35 mg/1OralCaraco Pharma, Inc.2009-08-14Not applicableUs
FibricorTablet35 mg/1OralTribute Pharmaceuticals2015-07-30Not applicableUs
FibricorTablet35 mg/1OralAralez Pharmaceuticals Us Inc.2017-08-05Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fenofibric acidCapsule, delayed release45 mg/1OralLupin Pharmaceuticals2013-12-17Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralZydus Pharmaceuticals Usa, Inc.2008-12-15Not applicableUs68382 0078 16 nlmimage10 c54062e3
Fenofibric AcidTablet35 mg/1OralMutual Pharmaceutical2009-08-31Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralAlembic Pharmaceuticals Inc.2017-05-15Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralActavis Pharma Company2016-01-21Not applicableUs
Fenofibric AcidCapsule, delayed release pellets45 mg/1OralMylan Pharmaceuticals2013-07-15Not applicableUs
Fenofibric AcidCapsule, delayed release pellets45 mg/1OralMylan Institutional2013-11-212016-10-31Us
Fenofibric AcidCapsule, delayed release135 mg/1OralZydus Pharmaceuticals Usa, Inc.2016-09-12Not applicableUs
Fenofibric AcidCapsule, delayed release135 mg/1OralAlembic Pharmaceuticals Limited2017-05-18Not applicableUs
Fenofibric AcidCapsule, delayed release45 mg/1OralAlembic Pharmaceuticals Inc.2017-05-15Not applicableUs
Categories
UNII
BGF9MN2HU1
CAS number
42017-89-0
Weight
Average: 318.75
Monoisotopic: 318.0658867
Chemical Formula
C17H15ClO4
InChI Key
MQOBSOSZFYZQOK-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoic acid
SMILES
CC(C)(OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1)C(O)=O

Pharmacology

Indication

For use as an adjunctive therapy to diet to: (a) reduce triglyceride levels in adult patients with severe hypertriglyceridemia, and (b) reduce elevated total cholesterol, low-density-lipoprotein (LDL-C), triglycerides, and apolipoprotein B, and to increase high-density-lipoprotein (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb). [Label]

Pharmacodynamics

Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis [Label]. Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis [Label]. Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C [Label].

Fenofibric acid, the active metabolite of fenofibrate, subsequently produces reductions in total cholesterol, LDL-C, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients [Label]. Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII [Label].

Mechanism of action

Having performed clinical studies with in vivo transgenic mice and in vitro human hepatocyte cultures, it is believed that the principal mechanism of action of fenofibric acid is demonstrated through its capability to activate peroxisome proliferator receptor alpha (PPAR-alpha) [Label].

By activating PPAR-alpha, fenofibric acid increases lipolysis and the elimination of triglyceride-rich particles from plasma by actuating lipoprotein lipase and reducing production of apoprotein C-III, which acts as an inhibitor of lipoprotein lipase activity [Label]. The resultant decrease in triglycerides causes an alteration in the size and composition of low-density-lipoprotein from small, dense particles to large, buoyant ones [Label]. The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly [Label]. Additionally, fenofibric acid's activation of PPAR-alpha also induces an increase in the synthesis of apoproteins apo A-I, apo A-II, and high-density-lipoprotein [Label].

Moreover, the use of fenofibric acid can also act to reduce serum uric acid levels in ordinary or hyperuricemic individuals by increasing the urinary excretion of uric acid [Label].

TargetActionsOrganism
APeroxisome proliferator-activated receptor alpha
agonist
Human
UMetalloproteinase
unknown
Human
UPeroxisome proliferator-activated receptor gammaNot AvailableHuman
UPeroxisome proliferator-activated receptor delta
unknown
Human
UNuclear receptor subfamily 1 group I member 2
partial agonist
Human
Absorption

Some studies have demonstrated that the bioavailability of fenofibric acid (a sample administration of 130 mg oral suspension to healthy volunteers about 4 hours after a light breakfast) is approximately 81% in the stomach, 88% in the proximal small bowel, 84% in the distal small bowel, and 78% in the colon [1]. Nevertheless, following the oral administration of fenofibric acid in healthy volunteers, median peak plasma levels for the drug occurred about 2.5 hours after administration [Label]. Moreover, exposure after administration of three 35 mg fenofibric acid tablets is largely comparable to that of one 105 mg tablet [Label].

Volume of distribution

The volume of distribution for fenofibric acid is demonstrated to be 70.9 +/- 27.5 L [2].

Protein binding

Fenofibric acid demonstrates serum protein binding of approximately 99% in ordinary and hyperlipidemic subjects [Label].

Metabolism

In vitro and in vivo metabolism studies reveal that fenofibric acid does not experience significant oxidative metabolism via the cytochrome P450 isoenzymes [Label]. The CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzymes are not known to play a role in the metabolism of fenofibric acid [Label].

Rather, fenofibric acid is predominantly conjugated with glucuronic acid and then excreted in urine [Label]. A small amount of fenofibric acid is reduced at the carbonyl moiety to benzhydrol metabolite which is, in turn, conjugated with glucuronic acid and excreted in urine [Label].

Route of elimination

Fenofibric acid metabolites are largely excreted in the urine [Label].

Half life

Following once daily dosing, fenofibric acid demonstrates an elimination associated with a half-life of about 20 hours after absorption [Label].

Clearance

In five elderly volunteers aged 77 to 87, the oral clearance of fenofibric acid after a single oral dose of fenofibrate was 1.2 L/h, which compares to 1.1 L/h in young adults [Label].

Toxicity

Oral LD50 (rat): 1242 mg/kg, Oral LD50 (mouse): 100 mg/kg, lntraperitoneal LD50 (mouse): 500 mg/kg [MSDS]

Fenofibric acid is contraindicated for: (a) patients with severe renal impairment, including those receiving dialysis, (b) patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities, (c) patients with preexisting gallbladder disease, (d) patients with known hypersensitivity to fenofibric acid or Fenofibrate, and (e) nursing mothers [Label].

The relationship between the use of fenofibric acid and risk of mortality and coronary heart disease morbidity has not been formally established [Label]. However, a number of studies involving fenofibrate and agents that are chemically and pharmacologically similar to fenofibrate demonstrate inconclusive results. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, a non-significant 11% (HR 1.11 [0.95, 1.29], p=0.18) and 19% (HR 1.19 [0.90, 1.57], p=0.22) increase in total and coronary heart disease mortality, respectively, with Fenofibrate as compared to placebo [Label]. For the Coronary Drug Project, a large study of post myocardial infarction of patients treated for 5 years with clofibrate, there was a difference in the rate of cholelithiasis and cholecystitis requiring surgery between the clofibrate and placebo groups of 3.0% vs. 1.8%, respectively [Label]. The World Health Organization (WHO) also conducted a study in which 5000 subjects without known coronary artery disease were treated with placebo or clofibrate for 5 years and followed for an additional year [Label]. The results involved a statistically significant, higher age-adjusted all-cause mortality in the clofibrate group compared with the placebo group (5.70% vs. 3.96%, p<0.01) in which excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis [Label]. With the Helsinki Heart Study, 4081 middle aged men without a history of coronary artery disease were given either placebo or gemfibrozil for 5 years, with a 3.5 year open extension afterward [Label]. Although total mortality was numerically higher in the gemfibrozil arm, it was statistically significant (p=0.19, 95% confidence interval for relative risk = 0.91-1.64). Finally, a secondary prevention component of the Helsinki Heart Study observed middle aged men not included in the primary prevention study because they had known or suspected coronary heart disease [Label]. When these subjects were administered gemfibrozil or placebo therapy for 5 years, cardiac deaths trended higher in the gemfibrozil group but was ultimately not statistically significant (HR 2.2, 95% confidence interval: 0.94-5.05) [Label].

Fibrates facilitate the risk for myopathy and have been associated with rhabdomyolysis [Label]. The risk for serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal failure, or hypothyroidism [Label]. Myopathy should be considered in any patient with diffuse myalgia, muscle tenderness or weakness, and/or marked elevations of creatine phosphokinase levels [Label].

Fenofibrate administered across a range of doses with the higher dose equivalent to 105 mg fenofibric acid has been associated with increases in serum transaminases like AST (SGOT) and ALT (SGPT) [Label]. In a pooled analysis of 10 placebo-controlled trials, increases to more than 3 times the upper limit of normal of ALT occurred in 5.3% of patients taking Fenofibrate versus 1.1% of patients treated with placebo [Label]. If enzyme levels persist above three times the normal limit, therapy is to be discontinued [Label]. After discontinuing fenofibrate treatment or during continued treatment a return to normal transaminase limits was usually observed [Label]. The incidence of increases in transaminases observed with fenofibrate therapy appear to be dose related [Label]. From an 8 week dose-ranging study, the incidence of ALT or AST elevations to at least three times the upper limit of normal was 13% in patients receiving dosages equivalent to 35 mg to 105 mg fenofibric acid per day and was comparatively 0% in those receiving placebo or doses equivalent to 35 mg or less fenofibric acid per day [Label]. Hepatocellular, chronic active and cholestatic hepatitis associated with Fenofibrate therapy have been reported after exposures of weeks to several years [Label]. In extremely rare cases, cirrhosis has been reported in associated with chronic active hepatitis [Label].

Increases in serum creatinine have been reported in patients on Fenofibrate [Label]. These elevations tend to return to baseline following discontinuation of the drug [Label]. Although the clinical significance of these observations is unknown, renal monitoring should be considered for patients with renal impairment and for patients at risk for renal insufficiency, perhaps like patients with diabetes or the elderly [Label].

Fenofibric acid may increase cholesterol excretion into the bile, leading to cholelithiasis [Label]. If gallstones are found, fenofibric acid should be discontinued [Label].

Caution must be exercised over the ability of fenofibric acid to potentiate the anticoagulant effects of coumarin anticoagulants, resulting in prolongation of the prothrombin time/International Normalized Ratio (PT/INR) [Label].

Pancreatitis has also been reported in patients taking Fenofibrate [Label]. This effect may be caused by the failure of efficacy in patients with severe hypertriglyceridemia, a direct drug effect, or a secondary phenomenon mediated through biliary tract stone or sludge formation with obstruction of the common bile duct [Label].

Mild to moderate hemoglobin, hematocrit, and white blood cell decreases have been observed in patients following the start of fenofibrate therapy [Label]. However, although these levels tend to stabilize during long-term administration of the medication [Label], thrombocytopenia and agranulocytosis have been observed in patients treated with fenofibrates as well [Label]. Scheduled monitoring of red and white blood cell counts during the first 12 months of fenofibric acid administration is subsequently recommended [Label].

Acute hypersensitivity reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis requiring patient hospitalization and treatment with steroids have been reported in patients treated with fenofibrates [Label].

In the fenofibrate arm during the FIELD trial, occurrences of pulmonary embolus (PE) and deep vein thrombosis (DVT) were recorded at higher rates when compared to the placebo group [Label]. In particular, the placebo group had N=4900 and the fenofibrate group N=4895 [Label]. For DVT there were 48 events (1%) in the placebo group and 67 (1%) in the fenofibrate group with p=0.074 [Label]. While for PE, there were 32 (0.7%) events in the placebo group and 53 (1%) in the fenofibrate group with p=0.022 [Label]. Likewise, in the Coronary Drug Project, a higher proportion of the clofibrate group reported definite or suspected fatal or nonfatal PE or thrombophlebitis when compared to the placebo group (5.2% vs 3.3% at 5 years with p<0.01) [Label].

Additionally there have been postmarketing and clinical trial reports of serious paradoxical decreases in HDL cholesterol levels to as low as 2 mg/dL happening in diabetic and non-diabetic patients initiated on fibrate therapy [Label]. This decrease in HDL-C is accompanied by a decrease in apolipoprotein A1. Such decreases have been reported to occur within 2 weeks to years after initiation of fibrate therapy [Label]. The HDL-C levels remain depressed until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is in fact rapid and sustained [Label]. HDL-C levels are recommended to be checked within the first few months after initiation of fibrate therapy. In the case of severely depressed HDL-C levels being detected, fibrate therapy should be withdrawn and HDL-C levels monitored until it has returned to baseline with no intention or plan to re-initiate fibrate therapy [Label].

Adverse effects associated with the use of fenofibrate and fenofibric acid include abdominal pain, back pain, headache, nausea, constipation, abnormal liver tests, increased AST, increased ALT, increased creatine phosphokinase, respiratory disorder, rhinitis, diarrhea, dyspepsia, nasopharyngitis, sinusitis, upper respiratory tract infection, arthralgia, myalgia, pain in extremity, and/or dizziness [Label].

Adverse effects identified during the post-approval use period of fenofibrate include rhabdomyolysis, panrcreatitis, renal failure, muscle spasms, acute renal failure, hepatitis, cirrhosis, anemia, asthenia, and severely depressed HDL-cholesterol levels [3].

As Fenofibric acid has the capability to potentiate the anticoagulant effect of coumarin anticoagulants (and subsequently prolong the PT/INR of patients), caution should be exercised when oral coumarin anticoagulants are given in conjunction with fenofibric acid. Frequent PT/INR determinations are therefore advisable until stabilized PT/INR readings are obtained [Label].

Fenofibric acid should be administered to patients at least 1 hour before or 4 to 6 hours after a bile acid resin is given as such drugs may bind other agents being given concurrently and impede their absorption [Label].

Immunosuppressant medications like cyclosporine and tacrolimus can cause nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the main elimination route for fenofibric acid, there exists a risk that an interaction could lead to deterioration of renal function [Label]. As a consequence, the benefits and risks of using fenofibric acid with any other potentially nephrotoxic agents should be carefully considered and the lowest effective dose employed [Label].

Cases of myopathy, including rhabdomyolysis, have been reported with fenofibrates co-administered with colchicine, and caution should be exercised when considering the combination use of fenofibrates with colchicine [Label].

No well controlled studies regarding the use of fenofibric acid in pregnant women have been established [Label]. Since the safety of fenofibric acid in pregnant women has not been formally elucidated, fenofibric acid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [Label].

Moreover, fenofibric acid should not be used in nursing mothers. Under the circumstances, a decision should be made between having to discontinue nursing or to discontinue the use of fenofibric acid, taking into perspective the importance of the drug therapy to the mother [Label].

The safety and effectiveness of fenofibric acid in paediatric patients has not been formally established [Label].

Fenofibric acid is predominantly excreted by the kidney system unchanged or as fenofibric acid glucuronide [Label]. The risk of experiencing adverse reactions associated with exposure to fenofibric acid may consequently be greater in patients with impaired renal function [Label]. Subsequently, because elderly patients may have a higher incidence of renal impairment, the dosage of fenofibric acid for geriatric patients should be based upon renal function, with normal renal function requiring no dosage modifications [Label]. Renal function monitoring in elderly patients taking fenofibric acid is recommended [Label].

In patients with severe renal impairment, the use of fenofibric acid is to be avoided while dose reductions is necessary in patients with mild to moderate renal impairment [Label]. Monitoring renal function in patients with renal impairment is recommended [Label].

The use of fenofibric acid has not been evaluated in patients with hepatic impairment [Label].

In a 24 month study, Wistar rats were dosed at various levels of fenofibrate. At a dose of 200mg/kg/day (6 times the maximum recommended human dose [MRHD] based on body surface area comparisons mg/m2), the incidence of liver carcinomas was significantly increased in both sexes of the rats [Label]. At doses of 10 (0.3 times the MRHD) and 200 mg/kg/day, a statistically significant increase in pancreatic carcinomas was observed in males, and an increase in pancreatic adenomas and benign testicular interstitial cell tumours were observed at 200 mg/kg/day in males [Label]. In a second 24 month study on the Sprague-Dawley strain of rats, doses of 10 and 60 mg/kg/day produced significant increases in the incidence of pancreatic acinar adenomas in both sexes of the rats and increases in interstitial cell tumours of the testes at 2 times the MRHD [Label].

In addition, fenofibrate 10 and 60 mg/kg/day, clofibrate 400 mg/kg/day (2 times the MRHD), and gemfibrozil 250 mg/kg/day (2 times the MRHD) are studied in a 117 week study in rats. Fenofibrate increased pancreatic acing adenomas in both sexes of the rats [Label]. Clofibrate increased hepatocellular carcinoma and pancreatic acinar adenomas in males and hepatic neoplastic nodules in females [Label]. And finally, gemfibrozil increased hepatic neoplastic nodules in males and females, while all three drugs increased testicular interstitial cell tumours in males [Label].

In a 21 month study with CF-1 mice, fenofibrate 10, 45, and 200 mg/kg/day (approximately 0.2, 1, and 3 times the MRHD) significantly increased the liver carcinomas in both sexes at 3 times the MRHD [Label]. With a second 18 month study at 10, 60, and 200 mg/kg/day, fenofibrate significantly increased the liver carcinomas in male and female mice 3 times the MRHD [Label].

Changes in peroxisome morphology and numbers have been observed in humans after treatment with other members of the fibrate class when liver biopsies were compared before and after treatment in the same individual [Label]

Fenofibrate was shown to be devoid of mutagenic potential in the Ames and micronucleus tests in vivo/rat [Label]. In addition, fenofibric acid, has bee.n demonstrated to be devoid of mutagenic potential in the following tests: Ames, mouse lymphoma, chromosomal aberration and sister chromatid exchange in human lymphocytes, and unscheduled DNA synthesis in primary rat hepatocytes [Label].

In a fertility study, rats were given oral dietary doses of fenofibrate. Males received doses for 61 days prior to mating and females for 15 days prior to mating through weaning, which resulted in no adverse effect on fertility at doses up to 300 mg/kg/day (~10 times the MRHD, based on mg/m2 surface area comparisons) [Label].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Fenofibric acid is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Fenofibric acid is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Fenofibric acid is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Fenofibric acid is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Fenofibric acid which could result in a higher serum level.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Fenofibric acid is combined with Acetohexamide.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Fenofibric acid which could result in a higher serum level.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Acipimox is combined with Fenofibric acid.
AcyclovirAcyclovir may decrease the excretion rate of Fenofibric acid which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Fenofibric acid which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Ling H, Luoma JT, Hilleman D: A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations. Cardiol Res. 2013 Apr;4(2):47-55. doi: 10.4021/cr270w. Epub 2013 May 9. [PubMed:28352420]
  2. Vlase L, Popa A, Muntean D, Leucuta SE: Pharmacokinetics and comparative bioavailability of two fenofibrate capsule formulations in healthy volunteers. Arzneimittelforschung. 2010;60(9):560-3. doi: 10.1055/s-0031-1296325. [PubMed:21117499]
  3. DailyMed Trilipix (fenofibric acid) delayed release capsule monogram [Link]
External Links
PubChem Compound
64929
PubChem Substance
347829325
ChemSpider
58457
BindingDB
28700
ChEBI
83469
ChEMBL
CHEMBL981
Wikipedia
Fenofibrate
ATC Codes
C10AB11 — Choline fenofibrate
FDA label
Download (468 KB)
MSDS
Download (24.2 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Capsule, delayed release pelletsOral135 mg/1
Capsule, delayed release pelletsOral45 mg/1
Capsule, delayed releaseOral45 mg/1
TabletOral105 mg/1
TabletOral35 mg/1
Capsule, delayed releaseOral135 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7259186No2005-01-072025-01-07Us
US7569612No2007-08-202027-08-20Us
US7741373No2007-08-202027-08-20Us
US7741374No2007-08-202027-08-20Us
US7915247No2007-08-202027-08-20Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0051 mg/mLALOGPS
logP3.97ALOGPS
logP4.36ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.1ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity83.19 m3·mol-1ChemAxon
Polarizability32.42 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-3649af6f9c4b41b005f1
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-32a876d779b641e3efe5
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-7f472b5dbad132612d0f
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-7d336fa21123052b7639
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-c719e39f8727bb7b4a81
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-d679eb2c4a1fd6add4da
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-315f65e0bc37c818bb8a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-32a876d779b641e3efe5
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-32a876d779b641e3efe5
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-025493f1f9167267c269
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-6a4de28c55a429fcb2dc
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0090000000-3649af6f9c4b41b005f1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01c0-0049000000-4fde30c6366aaf26d77b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0090000000-ef34ffdf5196e70b8a31
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0019-0980000000-3ad6ba9802e2a2b7b641
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0910000000-b963e54c4d24ec26b369
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0900000000-048d283cdc91de474403
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0090000000-37c84c25e65d613b9ce6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0039000000-9bde2b9a05392bcf9a07
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0090000000-4ca50e189c23da26c95f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001r-0890000000-0deb0153634d8254fbf7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-a9899a3039e6e594019f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-e09a6ff2195f97b9e36a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-d3a8a6509bfc59986717
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0039000000-9877282b22141d22ef61
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0090000000-49eb13bf6ac8b940026a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001r-0980000000-b3128b9adac2ce9ef4a0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-6957ae9ec970a7a430e7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-e6ede86247f2a517f635
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-8018d16193aeeecc196c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0090000000-ed51dbe03c7dbdb65df7

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzophenones
Direct Parent
Benzophenones
Alternative Parents
Diphenylmethanes / Aryl-phenylketones / Phenoxyacetic acid derivatives / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Monocarboxylic acids and derivatives
show 4 more
Substituents
Benzophenone / Aryl-phenylketone / Diphenylmethane / Phenoxyacetate / Phenoxy compound / Aryl ketone / Phenol ether / Benzoyl / Alkyl aryl ether / Chlorobenzene
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid, aromatic ketone, chlorobenzophenone (CHEBI:83469)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Unknown
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
mmp20
Uniprot ID
O43923
Uniprot Name
Matrix metalloproteinase-25
Molecular Weight
20353.66 Da
References
  1. Duhaney TA, Cui L, Rude MK, Lebrasseur NK, Ngoy S, De Silva DS, Siwik DA, Liao R, Sam F: Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload. Hypertension. 2007 May;49(5):1084-94. Epub 2007 Mar 12. [PubMed:17353509]
  2. Lebrasseur NK, Duhaney TA, De Silva DS, Cui L, Ip PC, Joseph L, Sam F: Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension. Hypertension. 2007 Sep;50(3):489-96. Epub 2007 Jul 2. [PubMed:17606858]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, Katayama S: Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. [PubMed:11779144]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
References
  1. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, Katayama S: Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. [PubMed:11779144]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Creusot N, Kinani S, Balaguer P, Tapie N, LeMenach K, Maillot-Marechal E, Porcher JM, Budzinski H, Ait-Aissa S: Evaluation of an hPXR reporter gene assay for the detection of aquatic emerging pollutants: screening of chemicals and application to water samples. Anal Bioanal Chem. 2010 Jan;396(2):569-83. doi: 10.1007/s00216-009-3310-y. Epub 2009 Nov 29. [PubMed:20024649]

Drug created on July 08, 2017 22:12 / Updated on October 01, 2018 16:44