Identification

Name
Pirfenidone
Accession Number
DB04951
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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 185.2218
Monoisotopic: 185.084063979
Chemical Formula
C12H11NO
Synonyms
  • pirfenidona
  • Pirfenidone
External IDs
  • AMR-69

Pharmacology

Indication

For the treatment of idiopathic pulmonary fibrosis (IPF).

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pirfenidone 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 action

Pirfenidone 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.

TargetActionsOrganism
UFurinNot AvailableHumans
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life

2-2.5 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Generally well tolerated with the most frequent side effects reported being photosensitivity rash and gastrointestinal symptoms.

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Pirfenidone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pirfenidone can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Pirfenidone can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Pirfenidone.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Pirfenidone.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Pirfenidone.
AdalimumabThe metabolism of Pirfenidone can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pirfenidone.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Pirfenidone.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Pirfenidone.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take at the same time every day.
  • Take with food. This may reduce the adverse effects of nausea and dizziness. Food also impacts the bioavailability of pirfenidone.

Products

Purchasing individual compounds or compound libraries for your research?
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EsbrietTablet, coated267 mg/1OralGenentech, Inc.2017-01-11Not applicableUS flag
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEU flag
EsbrietCapsule267 mgOralHoffmann La Roche2013-01-08Not applicableCanada flag
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEU flag
EsbrietCapsule267 mg/1OralGenentech, Inc.2014-10-15Not applicableUS flag
EsbrietTablet801 mgOralHoffmann La Roche2017-07-26Not applicableCanada flag
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEU flag
EsbrietTablet, coated801 mg/1OralGenentech, Inc.2017-01-11Not applicableUS flag
EsbrietCapsule267 mg/1OralInter Mune2014-10-16Not applicableUS flag
EsbrietTablet267 mgOralHoffmann La Roche2017-07-26Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L04AX05 — Pirfenidone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Pyridinones
Alternative Parents
Methylpyridines / Dihydropyridines / Benzene and substituted derivatives / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Dihydropyridine / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Methylpyridine / Monocyclic benzene moiety / Organic nitrogen compound
show 6 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ring assembly, pyridone (CHEBI:32016)

Chemical Identifiers

UNII
D7NLD2JX7U
CAS number
53179-13-8
InChI Key
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

References

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]
PubChem Compound
40632
PubChem Substance
175426915
ChemSpider
37115
BindingDB
50005201
RxNav
1592254
ChEBI
32016
ChEMBL
CHEMBL1256391
ZINC
ZINC000000001958
Wikipedia
Pirfenidone
AHFS Codes
  • 48:02.00 — Antifibrotic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)3
4RecruitingTreatmentProgressive Idiopathic Pulmonary Fibrosis1
4Unknown StatusTreatmentAcute Kidney Injury (AKI) / Sepsis1
4Unknown StatusTreatmentDermatopolymyositis / Interstitial Lung Diseases (ILD)1
4Unknown StatusTreatmentSarcoidosis, Pulmonary1
3Active Not RecruitingTreatmentAlbuminuria / Nephropathy, Diabetic1
3CompletedTreatmentDiabetic Foot Ulcers (DFU)1
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)5
3RecruitingTreatmentDermatomyositis Interstitial Lung Disease (Dm-ILD)1
3RecruitingTreatmentNovel Coronavirus Pneumonia / Pirfenidone / Pneumonia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral267 mg/1
CapsuleOral267 mg
TabletOral267 mg
TabletOral801 mg
Tablet, coatedOral267 mg/1
Tablet, coatedOral801 mg/1
Tablet, film coatedOral267 MG
Tablet, film coatedOral534 MG
Tablet, film coatedOral801 MG
Tablet, coatedOral267 mg
Tablet, coatedOral801 mg
Capsule, coatedOral267 mg
CapsuleOral
Tablet, film coatedOral200 mg
CapsuleOral200 mg
Tablet, coatedOral400 mg
Tablet, coatedOral600 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7988994No2011-08-022026-09-22US flag
US7816383No2010-10-192030-01-08US flag
US8013002No2011-09-062030-01-08US flag
US8084475No2011-12-272030-01-08US flag
US8778947No2014-07-152033-08-30US flag
US7566729No2009-07-282029-04-22US flag
US7767225No2010-08-032026-09-22US flag
US7635707No2009-12-222029-04-22US flag
US7767700No2010-08-032027-12-18US flag
US8592462No2013-11-262029-04-22US flag
US8383150No2013-02-262026-09-22US flag
US8318780No2012-11-272030-01-08US flag
US8420674No2013-04-162027-12-18US flag
US7910610No2011-03-222030-01-08US flag
US8648098No2014-02-112030-01-08US flag
US8754109No2014-06-172030-01-08US flag
US8609701No2013-12-172029-04-22US flag
US8753679No2014-06-172026-09-22US flag
US7696236No2010-04-132027-12-18US flag
US9561217No2017-02-072022-01-25US flag
US10188637No2019-01-292037-03-28US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemAxon
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)

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-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-2900000000-b9809376eba9769e9bee

Targets

Kind
Protein
Organism
Humans
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
Uniprot Name
Furin
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]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Arai T, Inoue Y, Sasaki Y, Tachibana K, Nakao K, Sugimoto C, Okuma T, Akira M, Kitaichi M, Hayashi S: Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis. Respir Investig. 2014 Mar;52(2):136-43. doi: 10.1016/j.resinv.2013.09.002. Epub 2013 Oct 24. [PubMed:24636270]
  2. Pirfenidone FDA label [File]

Drug created on October 21, 2007 16:23 / Updated on November 23, 2020 09:08

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