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
Structure for Nintedanib (DB09079)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Decreased pulmonary function •••••••••••• ••••• ••••••• Treatment of Idiopathic pulmonary fibrosis •••••••••••• ••••• ••••••• Treatment of Chronic progressive fibrosing interstitial lung disease •••••••••••• ••••• ••••••• Used in combination to treat Locally advanced non-small cell lung carcinoma (nsclc) Regimen in combination with: Docetaxel (DB01248) •••••••••••• ••••• ••••••• Used in combination to treat Locally recurrent non-small cell lung carcinoma (nsclc) Regimen in combination with: Docetaxel (DB01248) •••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
Target Actions Organism AVascular endothelial growth factor receptor 1 inhibitorHumans AVascular endothelial growth factor receptor 2 inhibitorHumans AVascular endothelial growth factor receptor 3 inhibitorHumans APlatelet-derived growth factor receptor alpha inhibitorHumans APlatelet-derived growth factor receptor beta inhibitorHumans AFibroblast growth factor receptor 1 inhibitorHumans AFibroblast growth factor receptor 2 inhibitorHumans AFibroblast growth factor receptor 3 inhibitorHumans UReceptor-type tyrosine-protein kinase FLT3 inhibitorHumans UTyrosine-protein kinase Lck inhibitorHumans UTyrosine-protein kinase Lyn inhibitorHumans UProto-oncogene tyrosine-protein kinase Src inhibitorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Nintedanib can be increased when it is combined with Abametapir. Abatacept The metabolism of Nintedanib can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Nintedanib is combined with Abciximab. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Nintedanib. Abrocitinib The 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Nintedanib esylate 42F62RTZ4G 656247-18-6 MMMVNAGRWOJNMW-FJBFXRHMSA-N - International/Other Brands
- Vargatef (Boehringer-Ingelheim)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ofev Capsule 100 mg/1 Oral Boehringer Ingelheim Pharmaceuticals, Inc. 2014-10-15 Not applicable US 
Ofev Capsule 100 mg Oral Boehringer Ingelheim 2021-01-27 Not applicable EU 
Ofev Capsule 150 mg Oral Boehringer Ingelheim (Canada) Ltd Ltee 2015-06-29 Not applicable Canada 
Ofev Capsule 150 mg/1 Oral Boehringer Ingelheim Pharmaceuticals, Inc. 2014-10-15 Not applicable US Ofev Capsule 150 mg Oral Boehringer Ingelheim 2021-01-27 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Auro-nintedanib Capsule 100 mg Oral Auro Pharma Inc Not applicable Not applicable Canada Auro-nintedanib Capsule 150 mg Oral Auro Pharma Inc Not applicable Not applicable Canada Jamp Nintedanib Capsule 150 mg Oral Jamp Pharma Corporation Not applicable Not applicable Canada
Categories
- ATC Codes
- L01EX09 — Nintedanib
- Drug Categories
- Antifibrotic Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Kinase Inhibitor
- OCT1 inhibitors
- OCT1 substrates
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- UGT1A1 Substrates
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
- EMA Summary of Product Characteristics: Vargatef (nintedanib) soft capsules for oral use [Link]
- FDA New Indication Approval: Nintedanib [Link]
- External Links
- KEGG Drug
- D10481
- PubChem Compound
- 9809715
- PubChem Substance
- 310265007
- ChemSpider
- 7985471
- BindingDB
- 50026612
- 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);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Interstitial Lung Disease / Pulmonary Fibrosis / Respiratory Diseases 1 4 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Novel Coronavirus-induced Lung Fibrosis 1 4 Completed Treatment Idiopathic Pulmonary Fibrosis (IPF) 4 4 Recruiting Treatment Myositis Associated Interstitial Lund Disease (MA-ILD) 1 4 Recruiting Treatment Progressive Idiopathic Pulmonary Fibrosis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 100 mg/1 Capsule Oral 150 mg/1 Capsule Oral 150.00 mg Capsule Oral 100 mg Capsule Oral 150 mg Capsule, liquid filled Oral 150 mg Capsule, liquid filled Oral 100 mg Capsule Oral 100.000 mg Capsule, gelatin coated Oral 100 MG Capsule, gelatin coated Oral 150 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7989474 No 2011-08-02 2024-04-06 US US7119093 No 2006-10-10 2024-02-21 US US6762180 Yes 2004-07-13 2026-04-01 US US9907756 Yes 2018-03-06 2029-12-07 US US10105323 Yes 2018-10-23 2029-12-04 US US10154990 Yes 2018-12-18 2026-07-08 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0309 mg/mL ALOGPS logP 3.7 ALOGPS logP 2.79 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 10.86 Chemaxon pKa (Strongest Basic) 7.23 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 94.22 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 159.1 m3·mol-1 Chemaxon Polarizability 58.79 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 221.033 predictedDeepCCS 1.0 (2019) [M+H]+ 223.14182 predictedDeepCCS 1.0 (2019) [M+Na]+ 229.05345 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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
- SubstrateInhibitor
- 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
- 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]
- FDA Approved Drug Products: Ofev (nintedanib) capsules for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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
- 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