Nintedanib

Identification

Summary

Nintedanib is a triple angiokinase inhibitor indicated for the treatment of idiopathic pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and in combination with docetaxel for non-small cell lung cancer.

Brand Names
Ofev, Vargatef
Generic Name
Nintedanib
DrugBank Accession Number
DB09079
Background

Nintedanib is a small molecule kinase inhibitor used in the treatment of pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and non-small cell lung cancer (NSCLC).8,9 It was first approved for use in the United States in 2014.8 Within the spectrum of idiopathic pulmonary fibrosis treatment options, nintedanib is currently one of only two disease-modifying therapies available and indicated for the condition (the other being Pirfenidone) and as such is used as a first-line treatment following diagnosis to slow down the progressive loss of lung function.6 As a chemotherapeutic agent for NSCLC, nintedanib, in combination with Docetaxel, is reserved for patients who have tried and failed first-line chemotherapeutic options.9

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 539.6248
Monoisotopic: 539.253254569
Chemical Formula
C31H33N5O4
Synonyms
  • methyl (3Z)-3-[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}anilino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate
  • Nintedanib
External IDs
  • BIBF 1120
  • BIBF-1120
  • BIBF1120

Pharmacology

Indication

Nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF)8 and to slow declining pulmonary function in patients with systemic sclerosis-associated interstitial lung disease.10 It is also indicated for the treatment of chronic fibrosing interstitial lung diseases with a progressive phenotype.10

In the EU, under the brand name Vargatef, nintedanib is indicated in combination with docetaxel for the treatment of adult patients with metastatic, locally advanced, or locally recurrent non-small cell lung cancer of adenocarcinoma histology who have already tried first-line therapy.9

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofDecreased pulmonary function••••••••••••••••••••••••
Treatment ofIdiopathic pulmonary fibrosis••••••••••••••••••••••••
Treatment ofChronic progressive fibrosing interstitial lung disease••••••••••••••••••••••••
Used in combination to treatLocally advanced non-small cell lung carcinoma (nsclc)Regimen in combination with: Docetaxel (DB01248)••••••••••••••••••••••••
Used in combination to treatLocally recurrent non-small cell lung carcinoma (nsclc)Regimen in combination with: Docetaxel (DB01248)••••••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Nintedanib is a small molecule kinase inhibitor that inhibits upstream kinase activity to ultimately inhibit lung fibroblast proliferation and migration, as well as signalling pathways that promote the proliferation and survival of endothelial and perivascular cells in tumour tissues.8,9,5

Nintedanib poses a risk of drug-induced liver injury, especially within the first three months of therapy.8,9 Liver function tests should be conducted at baseline prior to beginning therapy, at regular intervals for the first three months of therapy, and as indicated thereafter in patients exhibiting symptoms of hepatic injury such as jaundice or right upper quadrant pain. It is not recommended to be used in patients with pre-existing moderate to severe hepatic impairment (Child Pugh class B or C).

Mechanism of action

Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease.8,9 The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fns-Like tyrosine kinase-3 (FLT3).8,9,5 Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.5

In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src.8,9,5 The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.5,7

TargetActionsOrganism
AVascular endothelial growth factor receptor 1
inhibitor
Humans
AVascular endothelial growth factor receptor 2
inhibitor
Humans
AVascular endothelial growth factor receptor 3
inhibitor
Humans
APlatelet-derived growth factor receptor alpha
inhibitor
Humans
APlatelet-derived growth factor receptor beta
inhibitor
Humans
AFibroblast growth factor receptor 1
inhibitor
Humans
AFibroblast growth factor receptor 2
inhibitor
Humans
AFibroblast growth factor receptor 3
inhibitor
Humans
UReceptor-type tyrosine-protein kinase FLT3
inhibitor
Humans
UTyrosine-protein kinase Lck
inhibitor
Humans
UTyrosine-protein kinase Lyn
inhibitor
Humans
UProto-oncogene tyrosine-protein kinase Src
inhibitor
Humans
Absorption

The absolute bioavailability of nintedanib is low at approximately 4.7%, likely owing to substantial first-pass metabolism and the effects of p-glycoprotein (P-gp) transporters.8,9,5 Tmax following oral administration is reached after approximately 2 hours in fasted patients and approximately 4 hours in fed patients, regardless of the food consumed.8,9 Administration of nintedanib following a high-fat, high-calorie meal resulted in an increase in Cmax by approximately 15% and an increase in AUC by approximately 20%.5 Age, body weight, and smoking status have been found to alter exposure to nintedanib, but these effects are not significant enough to warrant dose alterations.8,5

Volume of distribution

Nintedanib appears to follow biphasic disposition kinetics - the observed volume of distribution following intravenous administration is 1050 L8,9, indicating extensive distribution into peripheral tissues. In rats, nintedanib was shown to rapidly and homogeneously distribute into peripheral tissues with the exception of the CNS, suggestive of an inability of nintedanib to cross the blood-brain barrier.5

Protein binding

Plasma protein binding of nintedanib is high, with a bound fraction of 97.8%. Albumin is thought to be the major binding protein.8,9,5

Metabolism

Nintedanib is predominantly metabolized via hydrolytic cleavage by esterases to its principle metabolite, BIBF 1202, which then undergoes glucuronidation via UGT enzymes in the intestines and liver (specifically UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10) to form BIBF 1202 glucuronide.8,9,5 The CYP450 enzyme system plays a minor role in nintedanib metabolism, with CYP3A4 believed to be the main contributor - the major CYP-dependent metabolite of nintedanib, a demethylated metabolite termed BIBF 1053, could not be detected in plasma during pharmacokinetic studies and was found only in small quantities in the feces (approximately 4% of total dose).5 CYP-dependent metabolism of nintedanib accounts for roughly 5% of total drug metabolism, as opposed to 25% for esterase cleavage.8,9 Other minor metabolites, M7 and M8, are found in very small quantities in the urine (0.03% and 0.01%, respectively), though their origin and relevance is currently unclear.5

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Route of elimination

Nintedanib is eliminated primarily via fecal and biliary excretion, with 93.4% of radio labelled nintedanib found in feces within 120 hours following administration.8,9,5 Renal clearance accounts for a small portion of nintedanib's elimination, approximately 0.65% of the total dose, and excretion of unchanged nintedanib 48 hours after oral and intravenous doses was 0.05% and 1.4%, respectively.8,9,5

Half-life

The terminal elimination half-life of nintedanib is approximately 10-15 hours.9,5 In patients with idiopathic pulmonary fibrosis, the effective half-life of nintedanib has been estimated to be approximately 9.5 hours.8,5

Clearance

Nintedanib is has a high total plasma clearance of approximately 1390 mL/min and a renal clearance of 20 mL/min.8

Adverse Effects
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Toxicity

Experience with nintedanib overdose is limited, but patients who inadvertently received higher-than-intended doses during initial trials experienced adverse effects consistent with the known safety profile of nintedanib, for example elevated liver enzymes and significant gastrointestinal effects.8,9

There are no specific guidelines for the treatment of nintedanib overdose - in this case, therapy should be interrupted and general supportive measures employed as indicated.8,9

Pathways
Not Available
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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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 Nintedanib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Nintedanib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Nintedanib is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Nintedanib.
AbrocitinibThe serum concentration of Nintedanib can be increased when it is combined with Abrocitinib.
Food Interactions
  • Take with food. Co-administration with food improves absorption.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Nintedanib esylate42F62RTZ4G656247-18-6MMMVNAGRWOJNMW-FJBFXRHMSA-N
International/Other Brands
Vargatef (Boehringer-Ingelheim)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OfevCapsule100 mg/1OralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-15Not applicableUS flag
OfevCapsule100 mgOralBoehringer Ingelheim2021-01-27Not applicableEU flag
OfevCapsule150 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2015-06-29Not applicableCanada flag
OfevCapsule150 mg/1OralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-15Not applicableUS flag
OfevCapsule150 mgOralBoehringer Ingelheim2021-01-27Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Auro-nintedanibCapsule100 mgOralAuro Pharma IncNot applicableNot applicableCanada flag
Auro-nintedanibCapsule150 mgOralAuro Pharma IncNot applicableNot applicableCanada flag
Jamp NintedanibCapsule150 mgOralJamp Pharma CorporationNot applicableNot applicableCanada flag

Categories

ATC Codes
L01EX09 — Nintedanib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indolecarboxylic acids. These are compounds containing a carboxylic acid group linked to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxylic acids
Alternative Parents
Alpha amino acids and derivatives / N-piperazineacetamides / Anilides / Indolines / Aniline and substituted anilines / Secondary alkylarylamines / N-methylpiperazines / Vinylogous amides / Tertiary carboxylic acid amides / Methyl esters
show 10 more
Substituents
1,4-diazinane / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Anilide / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
methyl ester, aromatic amine, enamine, oxindole, aromatic ester, aromatic amide, N-alkylpiperazine (CHEBI:85164)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
G6HRD2P839
CAS number
656247-17-5
InChI Key
XZXHXSATPCNXJR-ZIADKAODSA-N
InChI
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-
IUPAC Name
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
SMILES
COC(=O)C1=CC=C2C(NC(=O)\C2=C(/NC2=CC=C(C=C2)N(C)C(=O)CN2CCN(C)CC2)C2=CC=CC=C2)=C1

References

Synthesis Reference

Gerald J. Roth, Armin Heckel, Florian Colbatzky, Sandra Handschuh, Jörg Kley, Thorsten Lehmann-Lintz, Ralf Lotz, Ulrike Tontsch-Grunt, Rainer Walter, and Frank Hilberg Journal of Medicinal Chemistry 2009 52 (14), 4466-4480 DOI: 10.1021/jm900431g

General References
  1. Keating GM: Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis. Drugs. 2015 Jul;75(10):1131-40. doi: 10.1007/s40265-015-0418-6. [Article]
  2. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  3. Mazzei ME, Richeldi L, Collard HR: Nintedanib in the treatment of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2015 Jun;9(3):121-9. doi: 10.1177/1753465815579365. Epub 2015 Apr 10. [Article]
  4. Stopfer P, Rathgen K, Bischoff D, Ludtke S, Marzin K, Kaiser R, Wagner K, Ebner T: Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers. Xenobiotica. 2011 Apr;41(4):297-311. doi: 10.3109/00498254.2010.545452. Epub 2011 Jan 4. [Article]
  5. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  6. Richeldi L, Collard HR, Jones MG: Idiopathic pulmonary fibrosis. Lancet. 2017 May 13;389(10082):1941-1952. doi: 10.1016/S0140-6736(17)30866-8. Epub 2017 Mar 30. [Article]
  7. Li LF, Kao KC, Liu YY, Lin CW, Chen NH, Lee CS, Wang CW, Yang CT: Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway. J Cell Mol Med. 2017 Nov;21(11):2937-2949. doi: 10.1111/jcmm.13206. Epub 2017 Jun 9. [Article]
  8. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
  9. EMA Summary of Product Characteristics: Vargatef (nintedanib) soft capsules for oral use [Link]
  10. FDA New Indication Approval: Nintedanib [Link]
KEGG Drug
D10481
PubChem Compound
9809715
PubChem Substance
310265007
ChemSpider
7985471
BindingDB
50026612
RxNav
1592737
ChEBI
85164
ChEMBL
CHEMBL502835
ZINC
ZINC000100014909
PDBe Ligand
XIN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nintedanib
PDB Entries
3c7q / 5maf / 5te0 / 6nec

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral100 mg/1
CapsuleOral150 mg/1
CapsuleOral150.00 mg
CapsuleOral100 mg
CapsuleOral150 mg
Capsule, liquid filledOral150 mg
Capsule, liquid filledOral100 mg
CapsuleOral100.000 mg
Capsule, gelatin coatedOral100 MG
Capsule, gelatin coatedOral150 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7989474No2011-08-022024-04-06US flag
US7119093No2006-10-102024-02-21US flag
US6762180Yes2004-07-132026-04-01US flag
US9907756Yes2018-03-062029-12-07US flag
US10105323Yes2018-10-232029-12-04US flag
US10154990Yes2018-12-182026-07-08US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0309 mg/mLALOGPS
logP3.7ALOGPS
logP2.79Chemaxon
logS-4.2ALOGPS
pKa (Strongest Acidic)10.86Chemaxon
pKa (Strongest Basic)7.23Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area94.22 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity159.1 m3·mol-1Chemaxon
Polarizability58.79 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0000090000-f18cac7251efc2885ad3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4s-0004190000-658c819b623d79b5bb8c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-0300190000-a6810589012e6e9e34bc
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0202490000-747eebdc6e7126182871
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-02u3-4924230000-288ba353512dd0a79d24
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-07be-2208940000-013b5feebdc1df0d17cd
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-221.033
predicted
DeepCCS 1.0 (2019)
[M+H]+223.14182
predicted
DeepCCS 1.0 (2019)
[M+Na]+229.05345
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-ce...
Gene Name
LCK
Uniprot ID
P06239
Uniprot Name
Tyrosine-protein kinase Lck
Molecular Weight
58000.15 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, respons...
Gene Name
LYN
Uniprot ID
P07948
Uniprot Name
Tyrosine-protein kinase Lyn
Molecular Weight
58573.595 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sh3/sh2 adaptor activity
Specific Function
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
Gene Name
SRC
Uniprot ID
P12931
Uniprot Name
Proto-oncogene tyrosine-protein kinase Src
Molecular Weight
59834.295 Da
References
  1. Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307. [Article]
  2. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  3. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A7
Uniprot ID
Q9HAW7
Uniprot Name
UDP-glucuronosyltransferase 1-7
Molecular Weight
59818.315 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A8
Uniprot ID
Q9HAW9
Uniprot Name
UDP-glucuronosyltransferase 1-8
Molecular Weight
59741.035 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
  2. FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0. [Article]

Drug created at June 24, 2015 11:32 / Updated at February 20, 2024 23:55