Identification

Name
Nintedanib
Accession Number
DB09079
Type
Small Molecule
Groups
Approved
Description

Nintedanib is a drug indicated for the treatment of idiopathic pulmonary fibrosis (IPF) 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. In addition, nintedanib inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT3 and nRTK inhibition to IPF efficacy is unknown.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease characterized by a progressive loss of lung function with worsening dyspnoea and cough. Development is thought to be instigated by repetitive lung injury (such as by cigarette smoke, industrial dusts, gastrooesophageal reflux and viral infection) leading to destruction of epithelial alveolar cells. Subsequent dysregulation of the repair process results in the proliferation/migration of fibroblasts and their differentiation into myofibroblasts, abnormal extracellular matrix deposition and excessive collagen accumulation in the lung interstitium and alveolar space, leading to progressive fibrosis and stiffening of the lungs. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) mediate various processes, including fibrogenesis and angiogenesis, and are implicated in the pathogenesis of IPF. By blocking substrate binding and downstream signalling cascades, nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of extracellular matrix.

Structure
Thumb
Synonyms
  • methyl (3Z)-3-[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}anilino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate
External IDs
BIBF 1120 / BIBF-1120 / BIBF1120
Product Ingredients
IngredientUNIICASInChI Key
Nintedanib esylate42F62RTZ4G656247-18-6MMMVNAGRWOJNMW-FJBFXRHMSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OfevCapsule100 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2015-06-29Not applicableCanada
OfevCapsule150 mg/1OralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-15Not applicableUs
OfevCapsule150 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2015-06-29Not applicableCanada
OfevCapsule100 mg/1OralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-15Not applicableUs
International/Other Brands
Vargatef (Boehringer-Ingelheim)
Categories
UNII
G6HRD2P839
CAS number
656247-17-5
Weight
Average: 539.6248
Monoisotopic: 539.253254569
Chemical Formula
C31H33N5O4
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)-2-hydroxy-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-3H-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

Pharmacology

Indication

Nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Associated Conditions
Pharmacodynamics

By competitively and reversibly inhibiting the adenosine triphosphate binding pocket of the receptor tyrosine kinases VEGFR, FGFR and PDGFR, nintedanib blocks the intracellular signalling needed for the proliferation, migration and transformation of fibroblasts.

Mechanism of action

Nintedanib is a small molecule 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. In addition, nintedanib inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT3 and nRTK inhibition to IPF efficacy is unknown.

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

Nintedanib reaches maximum plasma concentrations approximately 2 to 4 hours after administration, and absolute bioavailability is 4.7%.

Volume of distribution

1050 L

Protein binding

The in vitro protein binding of nintedanib in human plasma was high, with a bound fraction of 97.8%. Serum albumin is considered to be the major binding protein.

Metabolism

The prevalent metabolic reaction for nintedanib is hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202. BIBF 1202 is subsequently glucuronidated by UGT enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide. Only a minor extent of the biotransformation of nintedanib consisted of CYP pathways, with CYP 3A4 being the predominant enzyme involved. In vitro, CYP-dependent metabolism accounted for about 5% compared to about 25% ester cleavage.

Route of elimination

The major route of elimination of drug-related radioactivity after oral administration of [14C] nintedanib was via fecal/biliary excretion (93.4% of dose), and the majority was excreted as BIBF 1202. The contribution of renal excretion to the total clearance was low (0.65% of dose). The overall recovery was considered complete (above 90%) within 4 days after dosing.

Half life

9.5 hours

Clearance

Total plasma clearance after intravenous infusion was found to be 1390 mL/min, while renal clearance was found to be 20 mL/min.

Toxicity

The most common adverse reactions (>5%) reported during clinical trials include diarrhea, nausea, vomiting, abdominal pain, liver enzyme elevation, headache, decreased weight, decreased appetite, and hypertension. The most frequent serious adverse reactions reported in patients treated with nintedanib, more than placebo, were bronchitis (1.2% vs. 0.8%) and myocardial infarction (1.5% vs. 0.4%). The most common adverse events leading to death in patients treated with nintedanib, more than placebo, were pneumonia (0.7% vs. 0.6%), lung neoplasm malignant (0.3% vs. 0%), and myocardial infarction (0.3% vs. 0.2%). Nintedanib can also cause fetal harm when administered to a pregnant woman: if it is used during pregnancy, or if the patient becomes pregnant while taking nintedanib, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when (R)-warfarin is combined with Nintedanib.
(S)-WarfarinThe risk or severity of bleeding can be increased when (S)-Warfarin is combined with Nintedanib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Nintedanib.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when 4-hydroxycoumarin is combined with Nintedanib.
5-androstenedioneThe metabolism of Nintedanib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Nintedanib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Nintedanib.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Nintedanib.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Nintedanib.
AbemaciclibThe serum concentration of Nintedanib can be increased when it is combined with Abemaciclib.
Food Interactions
Not Available

References

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. [PubMed:26063212]
  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. [PubMed:18559524]
  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. [PubMed:25862013]
  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. [PubMed:21204634]
External Links
KEGG Drug
D10481
PubChem Compound
9809715
PubChem Substance
310265007
ChemSpider
7985471
BindingDB
50026612
ChEBI
85164
ChEMBL
CHEMBL502835
HET
XIN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nintedanib
ATC Codes
L01XE31 — Nintedanib
AHFS Codes
  • 48:02.00 — Antifibrotic Agents
PDB Entries
3c7q / 5maf / 5te0
FDA label
Download (484 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCervical Carcinoma / Colorectal Adenocarcinoma / Non-Squamous Non-Small Cell Lung Cancer / Platinum-refractory Ovarian Carcinoma / Renal Cell Adenocarcinoma1
1Active Not RecruitingTreatmentLung Cancers / Stage IB Non-Small Cell Lung Carcinoma AJCC v7 / Stage II Non-Small Cell Lung Cancer AJCC v7 / Stage IIA Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIB Non-Small Cell Lung Carcinoma AJCC v7 / Stage IIIA Non-Small Cell Lung Cancer AJCC v71
1CompletedNot AvailableMalignant Solid Tumours1
1CompletedTreatmentGenital Neoplasms, Female1
1CompletedTreatmentHealthy Volunteers6
1CompletedTreatmentHepatic Insufficiency1
1CompletedTreatmentHepatocellular,Carcinoma1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)6
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentNeoplasms4
1CompletedTreatmentProstatic Neoplasms1
1CompletedTreatmentTumors2
1Not Yet RecruitingTreatmentHeathy Volunteer1
1RecruitingTreatmentAcute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Fibroblast Growth Factor Basic Form Measurement / FLT3 Internal Tandem Duplication / Recurrent Adult Acute Myeloid Leukemia / Refractory Acute Myeloid Leukemia1
1RecruitingTreatmentCancer, Breast1
1RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1RecruitingTreatmentScleroderma, Systemic1
1SuspendedTreatmentPatients With Any Advanced Solid Tumors1
1TerminatedOtherLung Cancer Non-Small Cell Cancer (NSCLC)1
1TerminatedTreatmentCancer of the Ovary1
1, 2Not Yet RecruitingTreatmentAdenocarcinoma of the Lung / NSCLC, Recurrent1
1, 2RecruitingTreatmentCancer of Pancreas1
1, 2RecruitingTreatmentCutaneous Malignant Melanoma1
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non Small Cell Lung Cancer Metastatic1
1, 2RecruitingTreatmentRelapsed/Refractory Acute Myeloid Leukemia1
1, 2TerminatedTreatmentGlioblastoma Multiforme (GBM)1
1, 2Unknown StatusTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2Active Not RecruitingTreatmentCancer of the Ovary / Fallopian Tube Cancer1
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentCarcinoid Tumors / Metastatic Carcinoid Tumors / Neuroendocrine Neoplasms1
2Active Not RecruitingTreatmentColon Adenocarcinoma / Rectal Adenocarcinoma / Recurrent Colon Carcinoma / Recurrent Rectal Carcinoma / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer1
2Active Not RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Medullary Thyroid Cancer (MTC)1
2Active Not RecruitingTreatmentEsophagogastric Adenocarcinoma1
2Active Not RecruitingTreatmentNon-Small Cell Lung Cancer Recurrent / Squamous Cell Carcinoma of Lung / Stage III Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2Active Not RecruitingTreatmentRecurrent or Metastatic Salivary Gland Cancer of the Head and Neck1
2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentTransitional Cell Carcinoma1
2CompletedNot AvailableIdiopathic Pulmonary Fibrosis (IPF)1
2CompletedPreventionNeoplasms, Ovarian1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Oligoastrocytoma / Anaplastic Oligodendroglioma (AO) / Glioblastomas / Gliosarcoma1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
2CompletedTreatmentEndometrial Adenocarcinomas / Endometrial Adenosquamous Carcinoma / Endometrial Clear Cell Adenocarcinoma / Endometrial Mucinous Adenocarcinoma / Endometrial Serous Adenocarcinoma / Endometrial Squamous Cell Carcinoma / Endometrial Transitional Cell Carcinoma / Endometrial Undifferentiated Carcinoma / Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm / Recurrent Uterine Corpus Carcinoma1
2CompletedTreatmentHepatocellular,Carcinoma2
2CompletedTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Refractory Small cell lung cancer1
2CompletedTreatmentNeoplasms, Colorectal2
2CompletedTreatmentProstatic Neoplasms2
2CompletedTreatmentPulmonary Fibrosis2
2CompletedTreatmentRecurrent Glioblastoma1
2Not Yet RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Lung Transplant; Complications1
2RecruitingPreventionHNSCC / Neoplasms, Head and Neck1
2RecruitingSupportive CareRadiation-Induced Pneumonitis / Stage IIA Non-Small Cell Lung Carcinoma / Stage IIB Non-Small Cell Lung Carcinoma / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2RecruitingTreatmentAppendix Cancer1
2RecruitingTreatmentEndometrial Clear Cell Carcinoma / Ovarian Clear Cell Carcinoma1
2RecruitingTreatmentAdvanced thymic carcinoma / Lung Cancer Metastatic / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC) / Lung Cancers / Pleural Mesotheliomas1
2RecruitingTreatmentLymphangioleiomyomatosis1
2RecruitingTreatmentMalignant Pleural Mesothelioma (MPM)1
2RecruitingTreatmentNeoplasms, Lung1
2RecruitingTreatmentRecurrent Pleural Malignant Mesothelioma / Stage IV Pleural Mesothelioma1
2RecruitingTreatmentSoft Tissue Sarcoma (STS)1
2RecruitingTreatmentUterine Cervical Neoplasms1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentNeoplasms, Colorectal1
2WithdrawnTreatmentEsophagogastric Adenocarcinoma / Metastatic Disease / No Previous Chemotherapy for Metastatic Esophagogastric Cancer1
2WithdrawnTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Platinum-sensitive1
3Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
3Active Not RecruitingTreatmentLung Diseases, Interstitial1
3CompletedTreatmentAbdominal wall neoplasm / Neoplasms, Ovarian1
3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)2
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentMesothelioma1
3CompletedTreatmentNeoplasms, Colorectal1
3CompletedTreatmentPulmonary Fibrosis2
3CompletedTreatmentScleroderma, Systemic1
3Not Yet RecruitingTreatmentLung-transplant Recipients1
3RecruitingTreatmentLung Diseases, Interstitial1
3TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)4
4RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
Not AvailableActive Not RecruitingNot AvailableIdiopathic Pulmonary Fibrosis (IPF)1
Not AvailableActive Not RecruitingNot AvailablePulmonary Fibrosis1
Not AvailableNo Longer AvailableNot AvailableIdiopathic Pulmonary Fibrosis (IPF)2
Not AvailableNot Yet RecruitingNot AvailableIdiopathic Pulmonary Fibrosis (IPF)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral100 mg
CapsuleOral100 mg/1
CapsuleOral150 mg
CapsuleOral150 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7989474No2011-08-022024-04-06Us
US7119093No2006-10-102024-02-21Us
US6762180No2004-07-132020-12-10Us
US9907756No2018-03-062029-06-07Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0398 mg/mLALOGPS
logP3.29ALOGPS
logP2.4ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)-6.1ChemAxon
pKa (Strongest Basic)15ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.71 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity159.85 m3·mol-1ChemAxon
Polarizability59.7 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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Indolecarboxylic acid / Alpha-amino acid or derivatives / N-piperazineacetamide / Dihydroindole / Anilide / Aniline or substituted anilines / Secondary aliphatic/aromatic amine / N-methylpiperazine / N-alkylpiperazine / Monocyclic benzene moiety
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
methyl ester, aromatic amine, enamine, oxindole, aromatic ester, aromatic amide, N-alkylpiperazine (CHEBI:85164)

Targets

Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
4. Platelet derived growth factor receptor alpha
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:18559524]
5. Platelet derived growth factor receptor beta
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]
Kind
Protein
Organism
Human
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. [PubMed:18559524]

Enzymes

Kind
Protein
Organism
Human
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

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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

Drug created on June 24, 2015 05:32 / Updated on December 10, 2018 13:39