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Identification
NameNintedanib
Accession NumberDB09079
TypeSmall Molecule
GroupsApproved
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 Identifiers
  • BIBF 1120
  • BIBF-1120
  • BIBF1120
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ofevcapsule100 mg/1oralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-28Not applicableUs
Ofevcapsule150 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2015-06-29Not applicableCanada
Ofevcapsule100 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2015-06-29Not applicableCanada
Ofevcapsule150 mg/1oralBoehringer Ingelheim Pharmaceuticals, Inc.2014-10-28Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
VargatefBoehringer-Ingelheim
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Nintedanib Esylate
ThumbNot applicableDBSALT001111
Categories
UNIIG6HRD2P839
CAS number656247-17-5
WeightAverage: 539.6248
Monoisotopic: 539.253254569
Chemical FormulaC31H33N5O4
InChI KeyXZXHXSATPCNXJR-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=CC2=C(C=C1)\C(=C(\NC1=CC=C(C=C1)N(C)C(=O)CN1CCN(C)CC1)C1=CC=CC=C1)C(O)=N2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indolecarboxylic acids. These are compounds containing a carboxylic acid group linked to an indole.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndolecarboxylic acids and derivatives
Direct ParentIndolecarboxylic acids
Alternative Parents
Substituents
  • Indolecarboxylic acid
  • N-piperazineacetamide
  • Alpha-amino acid or derivatives
  • Dihydroindole
  • Benzylether
  • Substituted aniline
  • Benzoyl
  • N-alkylpiperazine
  • N-methylpiperazine
  • Aniline
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Monocyclic benzene moiety
  • Vinylogous amide
  • Methyl ester
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Lactam
  • Carboxylic acid ester
  • Carboxamide group
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Enamine
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationNintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).
PharmacodynamicsBy 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 actionNintedanib 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.
Related Articles
AbsorptionNintedanib reaches maximum plasma concentrations approximately 2 to 4 hours after administration, and absolute bioavailability is 4.7%.
Volume of distribution

1050 L

Protein bindingThe 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.

SubstrateEnzymesProduct
Nintedanib
Not Available
BIBF 1202Details
BIBF 1202
BIBF 1202 glucuronideDetails
Route of eliminationThe 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 life9.5 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.

ToxicityThe 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 organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral100 mg/1
Capsuleoral100 mg
Capsuleoral150 mg
Capsuleoral150 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6762180 No2000-12-102020-12-10Us
US7119093 No2004-02-212024-02-21Us
US7989474 No2004-04-062024-04-06Us
Properties
StateSolid
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesL01XE31
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (484 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Nintedanib.
AcenocoumarolThe risk or severity of adverse effects can be increased when Acenocoumarol is combined with Nintedanib.
ApixabanThe risk or severity of adverse effects can be increased when Apixaban is combined with Nintedanib.
ArgatrobanThe risk or severity of adverse effects can be increased when Argatroban is combined with Nintedanib.
BivalirudinThe risk or severity of adverse effects can be increased when Bivalirudin is combined with Nintedanib.
CarbamazepineThe serum concentration of Nintedanib can be decreased when it is combined with Carbamazepine.
Citric AcidThe risk or severity of adverse effects can be increased when Citric Acid is combined with Nintedanib.
ClarithromycinThe serum concentration of Nintedanib can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Nintedanib can be increased when it is combined with Cobicistat.
CrizotinibThe serum concentration of Nintedanib can be increased when it is combined with Crizotinib.
Dabigatran etexilateThe risk or severity of adverse effects can be increased when Dabigatran etexilate is combined with Nintedanib.
DalteparinThe risk or severity of adverse effects can be increased when Dalteparin is combined with Nintedanib.
DanaparoidThe risk or severity of adverse effects can be increased when Danaparoid is combined with Nintedanib.
DarunavirThe serum concentration of Nintedanib can be increased when it is combined with Darunavir.
DesirudinThe risk or severity of adverse effects can be increased when Desirudin is combined with Nintedanib.
DicoumarolThe risk or severity of adverse effects can be increased when Dicoumarol is combined with Nintedanib.
DronedaroneThe serum concentration of Nintedanib can be increased when it is combined with Dronedarone.
Edetic AcidThe risk or severity of adverse effects can be increased when Edetic Acid is combined with Nintedanib.
EdoxabanThe risk or severity of adverse effects can be increased when Edoxaban is combined with Nintedanib.
EnoxaparinThe risk or severity of adverse effects can be increased when Enoxaparin is combined with Nintedanib.
ErythromycinThe serum concentration of Nintedanib can be increased when it is combined with Erythromycin.
Ethyl biscoumacetateThe risk or severity of adverse effects can be increased when Ethyl biscoumacetate is combined with Nintedanib.
Fondaparinux sodiumThe risk or severity of adverse effects can be increased when Fondaparinux sodium is combined with Nintedanib.
FosphenytoinThe serum concentration of Nintedanib can be decreased when it is combined with Fosphenytoin.
HeparinThe risk or severity of adverse effects can be increased when Heparin is combined with Nintedanib.
ItraconazoleThe serum concentration of Nintedanib can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Nintedanib can be increased when it is combined with Ketoconazole.
LumacaftorThe serum concentration of Nintedanib can be decreased when it is combined with Lumacaftor.
NadroparinThe risk or severity of adverse effects can be increased when Nadroparin is combined with Nintedanib.
NilotinibThe serum concentration of Nintedanib can be increased when it is combined with Nilotinib.
PhenindioneThe risk or severity of adverse effects can be increased when Phenindione is combined with Nintedanib.
PhenobarbitalThe serum concentration of Nintedanib can be decreased when it is combined with Phenobarbital.
PhenprocoumonThe risk or severity of adverse effects can be increased when Phenprocoumon is combined with Nintedanib.
PhenytoinThe serum concentration of Nintedanib can be decreased when it is combined with Phenytoin.
PirfenidoneThe serum concentration of Nintedanib can be decreased when it is combined with Pirfenidone.
PrimidoneThe serum concentration of Nintedanib can be decreased when it is combined with Primidone.
RanolazineThe serum concentration of Nintedanib can be increased when it is combined with Ranolazine.
RifampicinThe serum concentration of Nintedanib can be decreased when it is combined with Rifampicin.
RitonavirThe serum concentration of Nintedanib can be increased when it is combined with Ritonavir.
RivaroxabanThe risk or severity of adverse effects can be increased when Rivaroxaban is combined with Nintedanib.
SaquinavirThe serum concentration of Nintedanib can be increased when it is combined with Saquinavir.
SulodexideThe risk or severity of adverse effects can be increased when Sulodexide is combined with Nintedanib.
TelaprevirThe serum concentration of Nintedanib can be increased when it is combined with Telaprevir.
TesmilifeneThe serum concentration of Nintedanib can be decreased when it is combined with Tesmilifene.
TinzaparinThe risk or severity of adverse effects can be increased when Tinzaparin is combined with Nintedanib.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Nintedanib.
VerapamilThe serum concentration of Nintedanib can be increased when it is combined with Verapamil.
WarfarinThe risk or severity of adverse effects can be increased when Warfarin is combined with Nintedanib.
Food InteractionsNot Available

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 survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation ...
Gene Name:
FLT1
Uniprot ID:
P17948
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 embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domai...
Gene Name:
KDR
Uniprot ID:
P35968
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 cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced pr...
Gene Name:
FLT4
Uniprot ID:
P35916
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 and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (...
Gene Name:
FGFR1
Uniprot ID:
P11362
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 apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an...
Gene Name:
FGFR2
Uniprot ID:
P21802
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 essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineraliz...
Gene Name:
FGFR3
Uniprot ID:
P22607
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. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or...
Gene Name:
FLT3
Uniprot ID:
P36888
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-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antig...
Gene Name:
LCK
Uniprot ID:
P06239
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, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending ...
Gene Name:
LYN
Uniprot ID:
P07948
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 receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including...
Gene Name:
SRC
Uniprot ID:
P12931
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 ]

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
Molecular Weight:
141477.255 Da
Comments
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Drug created on June 24, 2015 05:32 / Updated on June 24, 2016 01:51