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Identification
NamePirfenidone
Accession NumberDB04951
TypeSmall Molecule
GroupsInvestigational
Description

Pirfenidone is an orally active small molecule drug that may inhibit collagen synthesis, down regulate production of multiple cytokines and block fibroblast proliferation and stimulation in response to cytokines. Pirfenidone has demonstrated activity in multiple fibrotic conditions, including those of the lung, kidney and liver. It is being investigated by InterMune.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Esbrietcapsule267 mg/1oralGenentech, Inc.2014-10-16Not applicableUs
Esbrietcapsule267 mgoralHoffmann La Roche Limited2013-01-08Not applicableCanada
Esbrietcapsule267 mg/1oralInter Mune, Inc.2014-10-16Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIID7NLD2JX7U
CAS number53179-13-8
WeightAverage: 185.2218
Monoisotopic: 185.084063979
Chemical FormulaC12H11NO
InChI KeyInChIKey=ISWRGOKTTBVCFA-UHFFFAOYSA-N
InChI
InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3
IUPAC Name
5-methyl-1-phenyl-1,2-dihydropyridin-2-one
SMILES
CC1=CN(C(=O)C=C1)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassHydropyridines
Direct ParentPyridinones
Alternative Parents
Substituents
  • Methylpyridine
  • Pyridinone
  • Dihydropyridine
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of idiopathic pulmonary fibrosis (IPF).
PharmacodynamicsPirfenidone is a novel agent with anti-inflammatory, antioxidant, and antifibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF).
Mechanism of actionPirfenidone is an orally active, small molecule that shows a wide range of biologic activity. In vitro evidence has shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Pirfenidone leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin. In addition, pirfenidone reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-beta target gene and furin substrate involved in carcinogenesis.
Related Articles
AbsorptionRapidly absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life2-2.5 hours
ClearanceNot Available
ToxicityGenerally well tolerated with the most frequent side effects reported being photosensitivity rash and gastrointestinal symptoms.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.996
Caco-2 permeable+0.8614
P-glycoprotein substrateNon-substrate0.8193
P-glycoprotein inhibitor INon-inhibitor0.755
P-glycoprotein inhibitor IINon-inhibitor0.9177
Renal organic cation transporterNon-inhibitor0.8157
CYP450 2C9 substrateNon-substrate0.6638
CYP450 2D6 substrateNon-substrate0.8248
CYP450 3A4 substrateSubstrate0.6111
CYP450 1A2 substrateInhibitor0.9108
CYP450 2C9 inhibitorNon-inhibitor0.5982
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.7166
CYP450 3A4 inhibitorNon-inhibitor0.775
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7633
Ames testNon AMES toxic0.7652
CarcinogenicityNon-carcinogens0.8992
BiodegradationNot ready biodegradable0.9112
Rat acute toxicity2.1330 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9784
hERG inhibition (predictor II)Non-inhibitor0.6301
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral267 mg/1
Capsuleoral267 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7566729 No2009-04-222029-04-22Us
US7635707 No2009-04-222029-04-22Us
US7696236 No2007-12-182027-12-18Us
US7767225 No2006-09-222026-09-22Us
US7767700 No2007-12-182027-12-18Us
US7816383 No2010-01-082030-01-08Us
US7910610 No2010-01-082030-01-08Us
US7988994 No2006-09-222026-09-22Us
US8013002 No2010-01-082030-01-08Us
US8084475 No2010-01-082030-01-08Us
US8318780 No2010-01-082030-01-08Us
US8383150 No2006-09-222026-09-22Us
US8420674 No2007-12-182027-12-18Us
US8592462 No2009-04-222029-04-22Us
US8609701 No2009-04-222029-04-22Us
US8648098 No2010-01-082030-01-08Us
US8753679 No2006-09-222026-09-22Us
US8754109 No2010-01-082030-01-08Us
US8778947 No2013-08-302033-08-30Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility2.89 mg/mLALOGPS
logP2ALOGPS
logP2.14ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)-1.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area20.31 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity57 m3·mol-1ChemAxon
Polarizability20.28 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Hale ML, Margolin SB, Krakauer T, Roy CJ, Stiles BG: Pirfenidone blocks the in vitro and in vivo effects of staphylococcal enterotoxin B. Infect Immun. 2002 Jun;70(6):2989-94. [PubMed:12010989 ]
  2. Shi S, Wu J, Chen H, Chen H, Wu J, Zeng F: Single- and multiple-dose pharmacokinetics of pirfenidone, an antifibrotic agent, in healthy Chinese volunteers. J Clin Pharmacol. 2007 Oct;47(10):1268-76. [PubMed:17906160 ]
External Links
ATC CodesL04AX05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
CarbamazepineThe serum concentration of Pirfenidone can be decreased when it is combined with Carbamazepine.
CiprofloxacinThe serum concentration of Pirfenidone can be increased when it is combined with Ciprofloxacin.
DeferasiroxThe serum concentration of Pirfenidone can be increased when it is combined with Deferasirox.
FluvoxamineThe serum concentration of Pirfenidone can be increased when it is combined with Fluvoxamine.
GemfibrozilThe serum concentration of Pirfenidone can be increased when it is combined with Gemfibrozil.
MethoxsalenThe serum concentration of Pirfenidone can be increased when it is combined with Methoxsalen.
NintedanibThe serum concentration of Nintedanib can be decreased when it is combined with Pirfenidone.
OfloxacinThe serum concentration of Pirfenidone can be increased when it is combined with Ofloxacin.
PhenobarbitalThe serum concentration of Pirfenidone can be decreased when it is combined with Phenobarbital.
PrimaquineThe serum concentration of Pirfenidone can be increased when it is combined with Primaquine.
PrimidoneThe serum concentration of Pirfenidone can be decreased when it is combined with Primidone.
RifampicinThe serum concentration of Pirfenidone can be decreased when it is combined with Rifampicin.
StiripentolThe serum concentration of Pirfenidone can be increased when it is combined with Stiripentol.
TranylcypromineThe serum concentration of Pirfenidone can be increased when it is combined with Tranylcypromine.
VemurafenibThe serum concentration of Pirfenidone can be increased when it is combined with Vemurafenib.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine-type endopeptidase inhibitor activity
Specific Function:
Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.
Gene Name:
FURIN
Uniprot ID:
P09958
Molecular Weight:
86677.375 Da
References
  1. Burghardt I, Tritschler F, Opitz CA, Frank B, Weller M, Wick W: Pirfenidone inhibits TGF-beta expression in malignant glioma cells. Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7. Epub 2007 Jan 10. [PubMed:17234158 ]
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Drug created on October 21, 2007 16:23 / Updated on August 24, 2016 01:53