Identification

Name
Pirfenidone
Accession Number
DB04951
Type
Small Molecule
Groups
Approved, Investigational
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
Synonyms
Not Available
External IDs
AMR-69
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEu
EsbrietCapsule267 mgOralHoffmann La Roche2013-01-08Not applicableCanada
EsbrietTablet, coated267 mg/1OralGenentech, Inc.2017-01-11Not applicableUs
EsbrietTablet801 mgOralHoffmann La Roche2017-07-26Not applicableCanada
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEu
EsbrietCapsule267 mg/1OralGenentech, Inc.2014-10-15Not applicableUs
EsbrietTablet267 mgOralHoffmann La Roche2017-07-26Not applicableCanada
EsbrietCapsule267 mgOralRoche Registration Gmb H2011-02-28Not applicableEu
EsbrietTablet, coated801 mg/1OralGenentech, Inc.2017-01-11Not applicableUs
EsbrietCapsule267 mg/1OralInter Mune2014-10-16Not applicableUs
Categories
UNII
D7NLD2JX7U
CAS number
53179-13-8
Weight
Average: 185.2218
Monoisotopic: 185.084063979
Chemical Formula
C12H11NO
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

Pharmacology

Indication

For the treatment of idiopathic pulmonary fibrosis (IPF).

Associated Conditions
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 AvailableHuman
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
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
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with (4R)-limonene.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with 5-androstenedione.
AbataceptThe risk or severity of infection can be increased when Pirfenidone is combined with Abatacept.
AbirateroneThe serum concentration of Pirfenidone can be increased when it is combined with Abiraterone.
AceclofenacThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Acemetacin.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Pirfenidone.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Pirfenidone.
Food Interactions
Not Available

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]
External Links
PubChem Compound
40632
PubChem Substance
175426915
ChemSpider
37115
BindingDB
50005201
ChEBI
32016
ChEMBL
CHEMBL1256391
Wikipedia
Pirfenidone
ATC Codes
L04AX05 — Pirfenidone
AHFS Codes
  • 48:02.00 — Antifibrotic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedPreventionNeurofibromatosis Type 1 / Precancerous Conditions1
1CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
1RecruitingTreatmentCancer, Advanced / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / Metastatic Lung Cancer / Non-Squamous Non-Small Cell Neoplasm of Lung / Squamous Cell Carcinoma of Lung1
1RecruitingTreatmentGraft Versus Host Disease (GVHD) / Obliterative Bronchiolitis1
1, 2CompletedTreatmentChronic Kidney Disease (CKD) / Fibrosis1
1, 2CompletedTreatmentDiabetes Mellitus (DM) / Diabetic Nephropathies1
2Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2Active Not RecruitingTreatmentLung Diseases, Interstitial1
2CompletedNot AvailableIdiopathic Pulmonary Fibrosis (IPF) / Pulmonary Fibrosis1
2CompletedTreatmentAlbinism / Albinism, Oculocutaneous / Inborn Errors of Metabolism / Platelet Storage Pool Deficiency / Pulmonary Fibrosis1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Fibrosis1
2CompletedTreatmentFibrosis / Glomerulonephritis minimal lesion / Glomerulosclerosis, Focal Segmental / Proteinuria / Renal Failure1
2CompletedTreatmentHypertrophic Cardiomyopathy1
2CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)3
2CompletedTreatmentLeiomyomas / Uterine Leiomyomas1
2CompletedTreatmentNeurofibromatosis1
2CompletedTreatmentNeurofibromatosis 1 / Plexiform Neurofibroma1
2CompletedTreatmentSclerosis, Progressive Systemic1
2RecruitingTreatmentCardiac Failure1
2RecruitingTreatmentChronic Lung Allograft Dysfunction / Disorders Related to Lung Transplantation1
2RecruitingTreatmentInterstitial Lung Disease (ILD) / Scleroderma, Systemic1
2RecruitingTreatmentLung Transplant Rejection / Restrictive Chronic Lung Allograft Dysfunction1
2RecruitingTreatmentPulmonary Fibrosis1
2RecruitingTreatmentRheumatoid Arthritis Interstitial Lung Disease1
2Unknown StatusTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2Unknown StatusTreatmentRadiation Pneumonitis1
2, 3Not Yet RecruitingTreatmentSclerosis, Progressive Systemic1
2, 3RecruitingTreatmentCLAD, Bronchiolitis Obliterans / Disorders Related to Lung Transplantation / Obliterative Bronchiolitis1
2, 3RecruitingTreatmentExtrinsic Allergic Alveolitis / Pulmonary Fibrosis1
3Active Not RecruitingTreatmentAlbuminuria / Diabetic Nephropathies1
3Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
3CompletedTreatmentDiabetic Foot Ulcers (DFU)1
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)4
3RecruitingTreatmentKeloid Scars1
4CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)3
4Not Yet RecruitingTreatmentAcute Kidney Injury (AKI) / Sepsis1
4Not Yet RecruitingTreatmentDermatopolymyositis / Interstitial Lung Disease (ILD)1
4RecruitingTreatmentSarcoidosis, Pulmonary1
Not AvailableActive Not RecruitingNot AvailablePulmonary Fibrosis1
Not AvailableApproved for MarketingNot AvailableIdiopathic Pulmonary Fibrosis (IPF)1
Not AvailableCompletedNot AvailableIdiopathic Pulmonary Fibrosis (IPF)2
Not AvailableCompletedSupportive CareRadiation Fibrosis1
Not AvailableRecruitingNot AvailableIdiopathic Pulmonary Fibrosis (IPF)1
Not AvailableRecruitingTreatmentInterstitial Lung Disease (ILD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral267 mg
CapsuleOral267 mg/1
TabletOral267 mg
TabletOral801 mg
Tablet, coatedOral267 mg/1
Tablet, coatedOral801 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7988994No2006-09-222026-09-22Us
US7816383No2010-01-082030-01-08Us
US8013002No2010-01-082030-01-08Us
US8084475No2010-01-082030-01-08Us
US8778947No2013-08-302033-08-30Us
US7566729No2009-04-222029-04-22Us
US7767225No2006-09-222026-09-22Us
US7635707No2009-04-222029-04-22Us
US7767700No2007-12-182027-12-18Us
US8592462No2009-04-222029-04-22Us
US8383150No2006-09-222026-09-22Us
US8318780No2010-01-082030-01-08Us
US8420674No2007-12-182027-12-18Us
US7910610No2010-01-082030-01-08Us
US8648098No2010-01-082030-01-08Us
US8754109No2010-01-082030-01-08Us
US8609701No2009-04-222029-04-22Us
US8753679No2006-09-222026-09-22Us
US7696236No2007-12-182027-12-18Us
US9561217No2002-01-252022-01-25Us

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

Taxonomy

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
Dihydropyridine / Pyridinone / Methylpyridine / Monocyclic benzene moiety / Benzenoid / Heteroaromatic compound / Lactam / Azacycle / Organic nitrogen compound / Hydrocarbon derivative
show 6 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ring assembly, pyridone (CHEBI:32016)

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
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
Human
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 October 16, 2018 08:38