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=CC2=C(C=C1)\C(C(=O)N2)=C(\NC3=CC=C(C=C3)N(C)C(=O)CN4CCN(C)CC4)C5=CC=CC=C5.COC(=O)C6=CC7=C(C=C6)\C(C(=O)N7)=C(\NC8=CC=C(C=C8)N(C)C(=O)CN9CCN(C)CC9)C%10=CC=CC=C%10

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 C31H33N5O4
Molecular Weight 539.6248
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
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 C2H6O3S
Molecular Weight 110.132
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
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
1040
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
503
Targets

Targets

Primary TargetPharmacologyConditionPotency
Vascular endothelial growth factor receptor 1
44
Target ID: P17948|||B3FR89
Gene ID: 2321.0
Gene Symbol: FLT1
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 34.0 nM [IC50]
Vascular endothelial growth factor receptor 2
112
Target ID: P35968
Gene ID: 3791.0
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 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
8504
 13.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
OFEV

Approved Use

Indicated for the treatment of idiopathic pulmonary fibrosis (IPF)

Launch Date

2014
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
34.8 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20028771/
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
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
171 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20028771/
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
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
16.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/20028771/
150 mg 2 times / day steady-state, oral
dose: 150 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.5 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
150 mg 2 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: FED
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
150 mg 2 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
NINTEDANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: FED
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
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
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)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
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
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
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
Health Status: unhealthy
Age Group: adult
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
Health Status: unhealthy
Age Group: adult
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
Health Status: unhealthy
Age Group: adult
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
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
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
Health Status: unhealthy
Age Group: 61 years
Sex: M+F
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)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
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)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000CrossR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
unhealthy, 67 years (range: 42 - 89 years)
Health Status: unhealthy
Age Group: 67 years (range: 42 - 89 years)
Sex: M+F
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205832Orig1s000MedR.pdf
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
Health Status: unhealthy
Age Group: adult
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
Health Status: unhealthy
Age Group: adult
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252

inducer
1087
inhibitor
2438

inducer
440
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2A6
879

CYP2B6
926

CYP2C8
1057

CYP2C19
2057

CYP2E1
1060

CYP4A11
21

UGT1A1
246

UGT2B7
197

OCT2
779

OCT1
620

OAT1
725

OAT2
153

MRP2
499

BCRP
910

P-gp
1741
P-gp
2052

UGT1A1
479

UGT1A7
249

UGT1A8
323

UGT1A10
331

esterase
74

OCT2
434

MRP2
252

BCRP
697

OCT1
393
CYP1A2
832

CYP2B6
669

CYP2C8
198

CYP2C19
329
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OCT1
656
 no [IC50 16 uM]
BIBF 1202
3
UGT1A1
303
 no [IC50 24.5 uM]
UGT1A1
303
 no [IC50 24.5 uM]
BIBF 1202
3
CYP3A4
2633
 no [IC50 70.1 uM]
UGT2B7
210
 no [IC50 77.6 uM]
CYP2C9
2497
 no [IC50 85.5 uM]
BIBF 1202 glucuronide
3
UGT2B7
210
 no [IC50 >200 uM]
BIBF 1202
3
BCRP
985
 no
BIBF 1202 glucuronide
3
CYP1A2
2333
 no
CYP1A2
2333
 no
CYP2A6
911
 no
CYP2B6
1160
 no
CYP2B6
1160
 no
CYP2C19
2141
 no
CYP2C19
2141
 no
CYP2C8
1117
 no
CYP2C8
1117
 no
CYP2C9
2497
 no
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP2E1
1146
 no
CYP3A4
2633
 no
CYP4A11
25
 no
MRP2
625
 no
MRP2
625
 no
BIBF 1202
3
OAT1
730
 no
OAT2
155
 no
OCT2
782
 no
OCT2
782
 no
BIBF 1202
3
P-gp
1932
 no
BIBF 1202
3
BCRP
985
 weak
BCRP
985
 weak
BIBF 1202
3
MRP2
625
 weak
BIBF 1202 glucuronide
3
P-gp
1932
 weak
BIBF 1202 glucuronide
3
OCT1
656
 yes [IC50 0.88 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
esterase
74
 major
CYP3A4
1946
 minor
BCRP
697
 no
BCRP
697
 no
BIBF 1202
3
MRP2
252
 no
MRP2
252
 no
BIBF 1202
3
OCT1
393
 no
BIBF 1202
3
OCT2
434
 no
OCT2
434
 no
BIBF 1202
3
P-gp
2052
 no
BIBF 1202
3
BCRP
697
 yes
BIBF 1202 glucuronide
3
MRP2
252
 yes
BIBF 1202 glucuronide
3
OCT1
393
 yes
UGT1A1
479
 yes
UGT1A10
331
 yes
UGT1A7
249
 yes
UGT1A8
323
 yes
P-gp
2052
 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
2263
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
Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis.
2015-07
Nintedanib in the treatment of idiopathic pulmonary fibrosis.
2015-06
Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis.
2014-09
A new hope for idiopathic pulmonary fibrosis.
2014-05-29
Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers.
2011-04
BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy.
2008-06-15
Patents

Patents

07119093
3
20040176392
3
JP2006524634A
46
JP2008525370A
3
JP4701159B2
91

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 Mon Mar 31 17:59:21 GMT 2025
Edited
by admin
on Mon Mar 31 17:59:21 GMT 2025
Record UNII
23O68KB9KV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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)
Preferred Name English
NINTEDANIB ESYLATE HEMIHYDRATE
Common Name English
Code System Code Type Description
CAS
959762-24-4
Created by admin on Mon Mar 31 17:59:21 GMT 2025 , Edited by admin on Mon Mar 31 17:59:21 GMT 2025
PRIMARY
SMS_ID
300000053465
Created by admin on Mon Mar 31 17:59:21 GMT 2025 , Edited by admin on Mon Mar 31 17:59:21 GMT 2025
PRIMARY
FDA UNII
23O68KB9KV
Created by admin on Mon Mar 31 17:59:21 GMT 2025 , Edited by admin on Mon Mar 31 17:59:21 GMT 2025
PRIMARY
Related Record Type Details
Structure of Nintedanib Esylate
ANHYDROUS->SOLVATE
Structure of Nintedanib
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of Nintedanib
ACTIVE MOIETY
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