U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula 2C31H33N5O4.2C2H6O3S.H2O
Molecular Weight 1317.529
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of NINTEDANIB ESYLATE HEMIHYDRATE

SMILES

O.CCS(O)(=O)=O.CCS(O)(=O)=O.COC(=O)C1=CC=C2C(NC(=O)\C2=C(/NC3=CC=C(C=C3)N(C)C(=O)CN4CCN(C)CC4)C5=CC=CC=C5)=C1.COC(=O)C6=CC=C7C(NC(=O)\C7=C(/NC8=CC=C(C=C8)N(C)C(=O)CN9CCN(C)CC9)C%10=CC=CC=C%10)=C6

InChI

InChIKey=FXFVOZKAPICGNY-NKYWIEMRSA-N
InChI=1S/2C31H33N5O4.2C2H6O3S.H2O/c2*1-34-15-17-36(18-16-34)20-27(37)35(2)24-12-10-23(11-13-24)32-29(21-7-5-4-6-8-21)28-25-14-9-22(31(39)40-3)19-26(25)33-30(28)38;2*1-2-6(3,4)5;/h2*4-14,19,32H,15-18,20H2,1-3H3,(H,33,38);2*2H2,1H3,(H,3,4,5);1H2/b2*29-28-;;;

HIDE SMILES / InChI
Molecular Formula C2H6O3S
Molecular Weight 110.132
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C31H33N5O4
Molecular Weight 539.6248
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=24782550; http://www.ncbi.nlm.nih.gov/pubmed/?term=21204634; http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2016/6-6-2016-boehringer-ingelheim-inventiva-collaborate-develop-potential-new-treatments-idiopathic-pulmonary-fibrosis.html

Nintedanib is a receptor tyrosine kinase inhibitor with potential antiangiogenic and antineoplastic activities. It is the only kinase inhibitor drug approved to treat idiopathic pulmonary fibrosis. that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fms-like tyrosine kinase-3 (FLT3). Among them, FGFR, PDGFR, and VEGFR have been implicated in IPF pathogenesis. Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts representing essential mechanisms of the IPF pathology.

CNS Activity

CNS Non-penetrant
1014
Curator's Comment: Nintedanib (molecular weight 539 Da) does not cross the blood–brain barrier in normal rat brain (investigator’s brochure U03-1563), as is generally expected for molecules [300 Da].

Originator

Approval Year

2014
494
Targets

Targets

Primary TargetPharmacologyConditionPotency
Vascular endothelial growth factor receptor 1
41
Target ID: P17948|||B3FR89
Gene ID: 2321.0
Gene Symbol: FLT1
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 34.0 nM [IC50]
Vascular endothelial growth factor receptor 2
104
Target ID: P35968
Gene ID: 3791.0
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 21.0 nM [IC50]
Vascular endothelial growth factor receptor 3
41
Target ID: P35916
Gene ID: 2324.0
Gene Symbol: FLT4
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 13.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
OFEV

Approved Use

Indicated for the treatment of idiopathic pulmonary fibrosis (IPF)

Launch Date

2014
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.4 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27093880
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
56.2 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27093880
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.7 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/27093880
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2.2%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
NINTEDANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day steady, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
unhealthy, 61 years
n = 6
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
DLT: Gamma-glutamyltransferase increased...
Dose limiting toxicities:
Gamma-glutamyltransferase increased (grade 3, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
250 mg 1 times / day steady, oral
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
unhealthy, 61 years
n = 4
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
DLT: Gamma-glutamyltransferase increased...
Dose limiting toxicities:
Gamma-glutamyltransferase increased (grade 3, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Disc. AE: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (5%)
Nausea (2%)
Decreased appetite (2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
Disc. AE: Weight decreased, Alanine aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Weight decreased (1.1%)
Alanine aminotransferase increased (0.6%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Disc. AE: Vomiting, Abdominal pain...
AEs leading to
discontinuation/dose reduction:
Vomiting (1%)
Abdominal pain (1%)
Asthenia (0.7%)
Hepatic enzyme increased (0.6%)
Aspartate aminotransferase increased (0.4%)
Blood bilirubin increased (0.4%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Disc. AE: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (10.9%)
Nausea (2.1%)
Decreased appetite (0.8%)
Weight decreased (0.6%)
Abdominal pain (0.8%)
Abdominal pain upper (0.8%)
Transaminases increased (0.4%)
Hepatic function abnormal (0.7%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
250 mg 2 times / day steady, oral
MTD
Dose: 250 mg, 2 times / day
Route: oral
Route: steady
Dose: 250 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25795637
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: adult
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/25795637
DLT: Elevated liver enzymes...
Dose limiting toxicities:
Elevated liver enzymes (grade 3, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25795637
600 mg 1 times / day multiple, oral
Overdose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, adult
n = 1
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Other AEs: Nasopharyngitis...
Other AEs:
Nasopharyngitis
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
600 mg 2 times / day multiple, oral
Overdose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: cancer
Age Group: adult
Population Size: 2
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Gamma-glutamyltransferase increased grade 3, 1 patient
DLT
200 mg 1 times / day steady, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
unhealthy, 61 years
n = 6
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
Gamma-glutamyltransferase increased grade 3, 1 patient
DLT
250 mg 1 times / day steady, oral
Dose: 250 mg, 1 times / day
Route: oral
Route: steady
Dose: 250 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
unhealthy, 61 years
n = 4
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/19846979
Decreased appetite 2%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Nausea 2%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Diarrhea 5%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Alanine aminotransferase increased 0.6%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
Weight decreased 1.1%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
Page: p. 15
Aspartate aminotransferase increased 0.4%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Blood bilirubin increased 0.4%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Hepatic enzyme increased 0.6%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Asthenia 0.7%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Abdominal pain 1%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Vomiting 1%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 87
Transaminases increased 0.4%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Weight decreased 0.6%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Hepatic function abnormal 0.7%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Abdominal pain upper 0.8%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Abdominal pain 0.8%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Decreased appetite 0.8%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Diarrhea 10.9%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Nausea 2.1%
Disc. AE
150 mg 2 times / day steady, oral
Recommended
Dose: 150 mg, 2 times / day
Route: oral
Route: steady
Dose: 150 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
unhealthy, 67 years (range: 42 - 89 years)
n = 723
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Population Size: 723
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
Page: p. 88
Elevated liver enzymes grade 3, 2 patients
DLT
250 mg 2 times / day steady, oral
MTD
Dose: 250 mg, 2 times / day
Route: oral
Route: steady
Dose: 250 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/25795637
unhealthy, adult
n = 11
Health Status: unhealthy
Condition: advanced solid tumors
Age Group: adult
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/25795637
Nasopharyngitis
600 mg 1 times / day multiple, oral
Overdose
Dose: 600 mg, 1 times / day
Route: oral
Route: multiple
Dose: 600 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
unhealthy, adult
n = 1
Health Status: unhealthy
Condition: idiopathic pulmonary fibrosis
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587

inducer
781
inhibitor
1767

inducer
389
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2B6
810

CYP2C8
911

CYP2C19
1478

CYP2E1
882

CYP4A11
21

UGT1A1
204

UGT2B7
146

OCT2
647

OCT1
512

OAT1
599

OAT2
145

MRP2
383

BCRP
699

P-gp
1461
P-gp
1537

UGT1A1
418

UGT1A7
236

UGT1A8
283

UGT1A10
291

esterase
72

OCT2
355

MRP2
205

BCRP
561

OCT1
327
CYP1A2
701

CYP2B6
547

CYP2C8
168

CYP2C19
293
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OCT1
543
 no [IC50 16 uM]
BIBF 1202
3
UGT1A1
254
 no [IC50 24.5 uM]
UGT1A1
254
 no [IC50 24.5 uM]
BIBF 1202
3
CYP3A4
1925
 no [IC50 70.1 uM]
UGT2B7
157
 no [IC50 77.6 uM]
CYP2C9
1819
 no [IC50 85.5 uM]
BIBF 1202 glucuronide
3
UGT2B7
157
 no [IC50 >200 uM]
BIBF 1202
3
BCRP
773
 no
BIBF 1202 glucuronide
3
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2B6
1001
 no
CYP2C19
1553
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
CYP4A11
25
 no
MRP2
475
 no
MRP2
475
 no
BIBF 1202
3
OAT1
603
 no
OAT2
147
 no
OCT2
648
 no
OCT2
648
 no
BIBF 1202
3
P-gp
1650
 no
BIBF 1202
3
BCRP
773
 weak
BCRP
773
 weak
BIBF 1202
3
MRP2
475
 weak
BIBF 1202 glucuronide
3
P-gp
1650
 weak
BIBF 1202 glucuronide
3
OCT1
543
 yes [IC50 0.88 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
esterase
72
 major
CYP3A4
1737
 minor
BCRP
561
 no
BCRP
561
 no
BIBF 1202
3
MRP2
205
 no
MRP2
205
 no
BIBF 1202
3
OCT1
327
 no
BIBF 1202
3
OCT2
355
 no
OCT2
355
 no
BIBF 1202
3
P-gp
1537
 no
BIBF 1202
3
BCRP
561
 yes
BIBF 1202 glucuronide
3
MRP2
205
 yes
BIBF 1202 glucuronide
3
OCT1
327
 yes
UGT1A1
418
 yes
UGT1A10
291
 yes
UGT1A7
236
 yes
UGT1A8
283
 yes
P-gp
1537
 yes
yes (co-administration study)
Comment: Coadministration with the P-gp and CYP3A4 inhibitor ketoconazole increased exposure of nintedanib by 1.61-fold based on AUC and 1.83-fold based on Cmax.
Page: 9.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:85164
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85164
ChemicalBook
CB72510401
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB72510401
ChemicalBook
CB92467147
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92467147
ChemicalBook
CB92469909
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92469909
MolPort
MolPort-009-679-380
https://www.molport.com/shop/molecule-link/MolPort-009-679-380
Selleck Chemicals
BIBF1120
http://www.selleckchem.com/products/BIBF1120.html
ZINC
ZINC000100014909
http://zinc15.docking.org/substances/ZINC000100014909
PubMed

PubMed

TitleDatePubMed
BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy.
2008 Jun 15
Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers.
2011 Apr
A new hope for idiopathic pulmonary fibrosis.
2014 May 29
Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis.
2014 Sep
Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis.
2015 Jul
Nintedanib in the treatment of idiopathic pulmonary fibrosis.
2015 Jun
Patents

Patents

07119093
3
20040176392
3
JP2006524634A
46
JP2008525370A
3
JP4701159B2
70

Sample Use Guides

In Vivo Use Guide
150 mg twice daily approximately 12 hours apart taken with food. Recommended dosage in patients with mild hepatic impairment: 100 mg twice daily approximately 12 hours apart taken with food. Consider temporary dose reduction to 100 mg, treatment interruption, or discontinuation for management of adverse reactions. Prior to treatment, conduct liver function tests and a pregnancy test
Route of Administration: Oral
In Vitro Use Guide
10-80 nmol/L resulted in 50% inhibition (EC50) of cell proliferation in human umbilical vascular endothelial cell HUVEC, microvascular skin endothelial cells HMSEC, umbilical artery smooth muscle cells HUASMC
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:30:16 GMT 2023
Edited
by admin
on Fri Dec 15 15:30:16 GMT 2023
Record UNII
23O68KB9KV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NINTEDANIB ESYLATE HEMIHYDRATE
Common Name English
1H-INDOLE-6-CARBOXYLIC ACID, 2,3-DIHYDRO-3-(((4-(METHYL(2-(4-METHYL-1-PIPERAZINYL)ACETYL)AMINO)PHENYL)AMINO)PHENYLMETHYLENE)-2-OXO-, METHYL ESTER, (3Z)-, METHANESULFONATE, HYDRATE (2:2:1)
Systematic Name English
Code System Code Type Description
CAS
959762-24-4
Created by admin on Fri Dec 15 15:30:16 GMT 2023 , Edited by admin on Fri Dec 15 15:30:16 GMT 2023
PRIMARY
FDA UNII
23O68KB9KV
Created by admin on Fri Dec 15 15:30:16 GMT 2023 , Edited by admin on Fri Dec 15 15:30:16 GMT 2023
PRIMARY
Related Record Type Details
Structure of NINTEDANIB ESYLATE
ANHYDROUS->SOLVATE
Structure of NINTEDANIB
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of NINTEDANIB
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