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Details

Stereochemistry ACHIRAL
Molecular Formula C31H33N5O4
Molecular Weight 539.6248
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of NINTEDANIB

SMILES

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

InChI

InChIKey=XZXHXSATPCNXJR-ZIADKAODSA-N
InChI=1S/C31H33N5O4/c1-34-15-17-36(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/h4-14,19,32H,15-18,20H2,1-3H3,(H,33,38)/b29-28-

HIDE SMILES / InChI

Molecular Formula C31H33N5O4
Molecular Weight 539.6248
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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

Approval Year

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

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 Oct 21 20:55:07 UTC 2019
Edited
by admin
on Mon Oct 21 20:55:07 UTC 2019
Record UNII
G6HRD2P839
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NINTEDANIB
DASH   INN   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
BIBF1120
Code English
INTEDANIB
MI  
Common Name English
BIBF 1120
Code English
NINTEDANIB COMPONENT OF OFEV
Brand Name English
METHYL (3Z)-3-(((4-(N-METHYL-2-(4-METHYLPIPERAZIN-1-YL)ACETAMIDO)PHENYL)AMINO)(PHENYL)METHYLIDENE)-2-OXO-2,3-DIHYDRO-1H-INDOLE-6-CARBOXYLATE
Systematic Name English
NINTEDANIB [WHO-DD]
Common Name English
NINTEDANIB [VANDF]
Common Name English
NINTEDANIB [USAN]
Common Name English
INTEDANIB [MI]
Common Name English
BIBF-1120
Code English
OFEV COMPONENT NINTEDANIB
Brand Name English
NINTEDANIB [INN]
Common Name English
VARGATEF
Brand Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS OFEV (AUTHORISED: IDIOPATHIC PULMONARY FIBROSIS)
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
FDA ORPHAN DRUG 344511
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
WHO-ATC L01XE31
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
FDA ORPHAN DRUG 528516
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
EU-Orphan Drug EU/3/16/1724
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
FDA ORPHAN DRUG 547916
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
NCI_THESAURUS C1742
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
NCI_THESAURUS C155727
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
Code System Code Type Description
EVMPD
SUB120728
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
MERCK INDEX
M6301
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY Merck Index
MESH
C530716
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
LactMed
656247-17-5
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
CAS
656247-17-5
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
ChEMBL
CHEMBL502835
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
IUPHAR
5936
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
DRUG BANK
DB09079
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
RXCUI
1592737
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY RxNorm
HSDB
656247-17-5
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
NCI_THESAURUS
C62765
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
PUBCHEM
9809715
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
INN
9229
Created by admin on Mon Oct 21 20:55:08 UTC 2019 , Edited by admin on Mon Oct 21 20:55:08 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
The urinary excretion of unchanged nintedanib within 48 h was about 1% of dose after intravenous administration. The major route of excretion of total [14C]-radioactivity was via feces, demonstrated by a fecal excretion of 93.4% of dose within 120 hours.
URINE
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Vss PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC