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Nintedanib

CAS No.
656247-17-5
Chemical Name:
Nintedanib
Synonyms
Intedanib;Nintedanib (BIBF 1120);INTEDANIB BASE;methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene;(3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate;methyl (3Z)-2-hydroxy-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-3H-indole-6-carboxylate;100837;Nidanib;NTEDANIB;Vargatef
CBNumber:
CB72510401
Molecular Formula:
C31H33N5O4
Molecular Weight:
539.64
MDL Number:
MFCD11974012
MOL File:
656247-17-5.mol
Last updated:2023-12-19 16:21:16

Nintedanib Properties

Melting point >237oC (dec.)
Boiling point 742.2±60.0 °C(Predicted)
Density 1.284±0.06 g/cm3(Predicted)
storage temp. Refrigerator
solubility DMSO (Slightly), Methanol (Slightly)
form Yellow solid.
pka 11.06±0.20(Predicted)
color Light Yellow to Light Green
InChIKey XZXHXSATPCNXJR-ZIADKAODSA-N
SMILES C(/C1C=CC=CC=1)(=C1\C(NC2=CC(C(=O)OC)=CC=C\12)=O)\NC1C=CC(N(C)C(=O)CN2CCN(C)CC2)=CC=1
FDA UNII G6HRD2P839
NCI Drug Dictionary nintedanib
ATC code L01EX09

Pharmacokinetic data

Protein binding 97.8%
Excreted unchanged in urine <1%
Volume of distribution 1050 Litres
Biological half-life 9-15

SAFETY

Risk and Safety Statements

Nintedanib price More Price(44)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 11022 BIBF 1120 ≥95% 656247-17-5 10mg $44 2024-03-01 Buy
Cayman Chemical 11022 BIBF 1120 ≥95% 656247-17-5 50mg $109 2024-03-01 Buy
Cayman Chemical 11022 BIBF 1120 ≥95% 656247-17-5 100mg $193 2024-03-01 Buy
Cayman Chemical 11022 BIBF 1120 656247-17-5 250mg $426 2024-03-01 Buy
Tocris 7049 Nintedanib ≥98%(HPLC) 656247-17-5 10 $59 2021-12-16 Buy
Product number Packaging Price Buy
11022 10mg $44 Buy
11022 50mg $109 Buy
11022 100mg $193 Buy
11022 250mg $426 Buy
7049 10 $59 Buy

Nintedanib Chemical Properties,Uses,Production

Description

Nintedanib is an oral administrated triple tyrosine kinase inhibitors developed by Boehringer Ingelheim, Germany. Its targets include platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and basic fiber (BFGF), being able to also inhibit the activation of MAPK and Akt. At present, it is mainly used for cancer treatment, such as colorectal cancer, ovarian cancer and multiple myeloma. The study regarding to the respiratory diseases mainly focuses on the clinical treatment of advanced non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). In June 2014, Boehringer Ingelheim has announced that the marketing authorization application of Nintedanib for the treatment of Idiopathic Pulmonary Fibrosis (IPF) had been confirmed by the European Medicines Agency (EMA) and been included in the accelerated approval list by the EMA.
Nintedanib

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.

indications

Nintedanib ( Vargatef ) is an oral triple angiokinase inhibitor which simultaneously inhibits vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR) signalling pathways. Growing scientific evidence shows that these three different angiokinase receptors play an important role not only in angiogenesis but also in tumour growth and metastasis.
Nintedanib is currently being investigated in patients with various solid tumours including Phase III studies in advanced NSCLC, colorectal cancer (refractory to standard treatment) and ovarian cancer, and also in Phase II studies in mesothelioma, kidney cancer (renal cell carcinoma) and liver cancer (hepatic cell carcinoma).
In the EU, nintedanib in the treatment of idiopathic pulmonary fibrosis (IPF) has recently received a positive CHMP opinion. The U.S. Food and Drug Administration (FDA) has approved nintedanib capsules under the brand name OFEV for oral use for the treatment of IPF.

Drugbank 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.
References
https://www.drugbank.ca/drugs/DB09079

Uses

It is an indolinone derivative potently blocking VEGF-, PDGF-, and FGF-receptor kinases; an indolinone as triple angiokinase inhibitors. An antitumor agent.

Uses

BIBF1120 (Vargatef) is a potent inhibitor of VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.

Definition

ChEBI: A member of the class of oxindoles that is a kinase inhibitor used (in the form of its ethylsulfonate salt) for the treatment of idiopathic pulmonary fibrosis and cancer.

Biological Activity

nintedanib (bibf 1120) is an indolinone-derived oral active, triple angiokinase inhibitor of vascular endothelial growth factor receptor (vegfr)1-3, fibroblast growth factor receptor (fgfr)1-3 and platelet-derived growth factor receptor (pdgfr)α/β1. it has shown potent antiangiogenic activity at nanomolar (ic50, 20-100 nmol/l) by blocking these receptor-mediated signaling pathways1,2. nintedanib (bibf 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis as these receptors have been shown to be potentially involved in the pathogenesis of pulmonary fibrosis3,4. as a novel angiogenesis inhibitor, it is also being widely evaluated in different cancer models and has displayed significant anti-tumor activities by inhibiting tumor blood vessel formation5-7.to further evaluate its antitumor effects on multiple tumors, nintedanib is currently entering several

Clinical Use

Tyrosine kinase inhibitor:
Treatment of locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology in combination with docetaxel
Treatment of Idiopathic Pulmonary Fibrosis (IPF)

target

VEGFR1/2/3

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration reduced by rifampicin - avoid.
Antifungals: concentration increased by ketoconazole.
Antipsychotics: increased risk of agranulocytosis with clozapine - avoid.

Metabolism

Nintedanib is metabolised in the liver, initially by hydrolytic cleavage by esterases and then by glucuronidation by uridine diphosphate glucuronosyltransferase enzymes. Only a minor portion is metabolised by cytochrome P450 isoenzymes, mainly CYP3A4. More than 90% of a dose is eliminated by faecal/biliary excretion.

storage

Store at -20°C

References

[1]hilberg, f. et al. bibf 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. cancer research 68, 4774-4782, doi:10.1158/0008-5472.can-07-6307 (2008).

656247-18-6
656247-17-5
Synthesis of Nintedanib from Nintedanib Ethanesulfonate Salt
Global( 377)Suppliers
Supplier Tel Email Country ProdList Advantage
SyncoZymes (Shanghai) Co., Ltd.,
+86-021-68187180-811 +86-13681683526 lchen@syncozymes.com China 188 58
HangZhou RunYan Pharma Technology Co.,LTD.
+86-88660901 +86-18112526015 sales@runyanpharma.com China 326 58
Wuhan Topule Biopharmaceutical Co., Ltd
+8618327326525 masar@topule.com China 8475 58
Hebei Mojin Biotechnology Co., Ltd
+86-13288715578 +86-13231137666 sales@hbmojin.com China 12409 58
Hebei Yanxi Chemical Co., Ltd.
+8617531190177 peter@yan-xi.com China 5960 58
shandong perfect biotechnology co.ltd
+86-53169958659; +8618596095638 sales@sdperfect.com China 294 58
Henan Tengmao Chemical Technology Co. LTD
+8615238638457 salesvip2@hntmhg.com China 401 58
Hangzhou ICH Biofarm Co., Ltd
+undefined8613073685410 sales@ichemie.com China 985 58
Capot Chemical Co.,Ltd.
571-85586718 +8613336195806 sales@capotchem.com China 29797 60
Nanjing Gold Pharmaceutical Technology Co. Ltd.
025-84209270 15906146951 CHINA 115 55

View Lastest Price from Nintedanib manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Nintedanib (BIBF 1120) pictures 2024-03-12 Nintedanib (BIBF 1120)
656247-17-5
US $0.00 / g 1g 98% HPLC 100kg shandong perfect biotechnology co.ltd
Nintedanib pictures 2024-01-20 Nintedanib
656247-17-5
US $9.90-1277.00 / g 10g 99.99%HPLC.USP42——Powder、Oil、Pills、Capsules、Tablets,Customized packaging 100KG/Month Wuhan Biocar Pharmacy Co., Ltd.
Nintedanib pictures 2023-12-19 Nintedanib
656247-17-5
US $0.00-0.00 / kg 1kg 99%, Single impurity<0.1 1 ton Nanjing Fred Technology Co., Ltd
  • Nintedanib pictures
  • Nintedanib
    656247-17-5
  • US $9.90-1277.00 / g
  • 99.99%HPLC.USP42——Powder、Oil、Pills、Capsules、Tablets,Customized packaging
  • Wuhan Biocar Pharmacy Co., Ltd.
  • Nintedanib pictures
  • Nintedanib
    656247-17-5
  • US $0.00-0.00 / kg
  • 99%, Single impurity<0.1
  • Nanjing Fred Technology Co., Ltd
Nintedanib Nintedanib/Intedanib/Vargatef BIBF 1120; VARGATEF; INTEDANIB;INTEDANIB BASE Intedanib Vargatef Nintedanib, Free Base, >99% methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate NTEDANIB (3Z)-2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-1H-Indole-6-carboxylic acid methyl ester methyl (Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate Methyl (Z)-3-[[[4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl]amino](phenyl)methylene]-2-oxoindoline-6-carboxylate BIBF-1120(Nintedanib,Vargatef) BIBF 1120; VARGATEF; INTEDANIB Vargatef Nintedanib whatsapp methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate Nintedanib (BIBF 1120) Vargatef (nintedanib) 3-[(4-{Methyl-[2-(4-methyl-piperazin-1-yl)-acetyl]-amino}-phenylamino)-phenyl-methylene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Nintedanib-016 100837 Nintedanib (Intedanib) Vargatef (BIBF 1120, Intedanib) NINTEDANIB; BIBF1120; VARGATEF; BIBF-1120 Nidanib BIBF1120;VARGATEF;BIBF-1120 Intedanib (Nintedanib) 1H-Indole-6-carboxylic acid, 2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-, methyl ester, (3Z)- Nidanib ethane sulfonate Nintedanib USP/EP/BP Nintedanib (Vargatef High purity CAS 656247-17-5 Nintedanib in stock INTEDANIB BASE Nintedanib (BIBF 1120) methyl (3Z)-2-hydroxy-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-3H-indole-6-carboxylate Intedanib methyl (3Z)-3-{[(4-{methyl[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)amino](phenyl)methylidene (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate FGFR,PDGFR,Nintedanib,Inhibitor,Platelet-derived growth factor receptor,Fibroblast growth factor receptor,Vascular endothelial growth factor receptor,VEGFR,BIBF1120,BIBF-1120,inhibit Methyl 2-hydroxy-3- N-[4-[methyl-[2-(4-methyIpiperazin- Methyl (Z)-3-[[[4-[N-Methyl-2-(4-methyl-1-piperazinyl)acetamido]phenyl]amino](phenyl)methylene]-2-oxoindoline-6-carboxylate 656247-17-5 C31H33O4N5 Heterocycles Intermediates & Fine Chemicals Pharmaceuticals Amines Nintedanib Inhibitors API API 656247-17-5