Nintedanib

製品コードS1010 バッチS101002

化学情報

	Synonyms	BIBF 1120, Intedanib	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₃₁H₃₃N₅O₄
	分子量	539.62	CAS No.	656247-17-5
Solubility (25°C)*	体外	DMSO	15 mg/mL (27.79 mM)
		Ethanol	4 mg/mL (7.41 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Nintedanib is a potent triple angiokinase inhibitor for 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 in cell-free assays. Phase 3.
in vitro	BIBF1120 inhibits PDGFR kinase activity of PDGFR alpha and PDGFR beta types with IC50 values of 59 nM and 65 nM, respectively. In addition, BIBF1120 suppresses the FGFR subtypes with IC50 of 60 nM, 37 nM and 108 nM for FGFR1, FGFR2, and FGFR3, respectively. BIBF1120 binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. The indolinone scaffold forms two hydrogen bonds with the backbone nitrogen of Cys⁹¹⁹ and the backbone carbonyl oxygen of Glu⁹¹⁷ in the hinge region. BIBF 1120 inhibits proliferation of PDGF-BB stimulated BRPs with EC50 of 79 nM in cell assays. BIBF1120 at concentrations as low as 100 nM blocks activation of MAPK after stimulation with 5% serum plus PDGF-BB. In cultures of human vascular smooth muscle cells (HUASMC), BIBF1120 prevents PDGF-BB stimulated proliferation with an EC50 of 69 nM. ^[1]
in vivo	In all tumor models tested thus far, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model, BIBF1120 is highly active at well-tolerated doses (25-100 mg/kg daily p.o.). This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth inhibition. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	VEGFR2 Kinase Assay
キナーゼアッセイ	The cytoplasmic tyrosine kinase domain of VEGFR2 (residues 797-1355 according to sequence deposited in databank SWISS-PROT P35968) is cloned into pFastBac fused to GST and extracted. Enzyme activity is assayed in the presence or absence of serial dilutions of BIBF1120 performed in 25% DMSO. Each microtiter plate contains internal controls such as blank, maximum reaction, and historical reference compound. All incubations are conducted at room temperature on a rotation shaker. 10 μL of each BIBF1120 dilution is added to 10 μL of diluted kinase (0.8 μg/mL VEGFR2, 10 mM Tris pH 7.5, 2 mM EDTA, and 2 mg/mL BSA) and preincubated for 1 hour. The reaction is started by addition of 30 μL of substrate mix containing 62.4 mM Tris pH 7.5, 2.7 mM DTT, 5.3 mM MnCl₂, 13.3 mM Mg-acetate, 0.42 mM ATP, 0.83 mg/mL Poly-Glu-Tyr(4:1), and 1.7 μg/mL Poly-Glu-Tyr(4:1)-biotin and incubated for 1 hour. The reaction is stopped by addition of 50 μL of 250 mM EDTA, 20 mM HEPES, pH 7.4. 90 μL of the reaction mix is transferred to a streptavidin plate and incubated for 1-2 hours. After three washes with PBS the EU-labeled antibody, PY20 is added (recommended dilution 1:2000 of 0.5 mg/mL labeled antibody in DELFIA assay buffer). Excessive detection antibody is removed by three washes of DELFIA washing buffer. Then 10 minutes before measurement on the multilabel reader, each well is incubated with 100 μL of DELFIA enhancement solution.
細胞アッセイ	細胞株	HUVEC, HUASMC, and BRP cell lines
	濃度	50 nM
	反応時間	2 hours
	実験の流れ	The cell lines HUVEC, HUASMC, and BRP are used for the assay. BIBF1120 is added to the cultures two hours before the addition of ligands. Cell lysates are generated. Western blotting is done using standard SDS-PAGE methods, loading 50 to 75 μg of protein per lane. Detection is facilitated by enhanced chemiluminescence. Total and phosphorylated mitogen-activated protein kinase (MAPK) is analyzed using monoclonal antibodies M3807 and M8159. Total Akt is detected using the corresponding polyclonal antibody and phosphorylated Akt (Ser473) is analyzed by using its monoclonal antibody. Monoclonal antibody is also used to detect cleaved caspase-3 while KDR (VEGFR2) protein is detected using a corresponding antibody.
動物実験	動物モデル	FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 xenografts in Athymic NMRI-nu/nu female mice
	投薬量	100 mg/kg
	投与方法	p.o.

参考

カスタマーフィードバック

: Data from [Cell Oncol , 2011, 34, 33–44]

: Data from [Cell Oncol , 2011, 34, 33–44]

: Data from [Cell Oncol , 2011, 34, 33–44]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting PDGF signaling of cancer-associated fibroblasts blocks feedback activation of HIF-1α and tumor progression of clear cell ovarian cancer [ Cell Rep Med, 2024, S2666-3791(24)00201-5]	PubMed: 38670097
Nintedanib Mitigates Radiation-Induced Pulmonary Fibrosis by Suppressing Epithelial Cell Inflammatory Response and Inhibiting Fibroblast-to-Myofibroblast Transition [ Int J Biol Sci, 2024, 20(9):3353-3371]	PubMed: 38993568
KRASG 12C-inhibitor-based combination therapies for pancreatic cancer: insights from drug screening [ Mol Oncol, 2024, 10.1002/1878-0261.13725]	PubMed: 39253995
Hypoxia Promotes Invadosome Formation by Lung Fibroblasts [ Cells, 2024, 13(13)1152]	PubMed: 38995003
Impact of Nintedanib and Anti-Angiogenic Agents on Uveal Melanoma Cell Behavior [ Invest Ophthalmol Vis Sci, 2024, 65(2):30]	PubMed: 38381412
Identification of aryl hydrocarbon receptor allosteric antagonists from clinically approved drugs [ Drug Dev Res, 2024, 85(5):e22232]	PubMed: 38992915
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells [ Cell Death Dis, 2023, 10.1038/s41419-023-06240-x]	PubMed: 37938546
Identification of Paired-related Homeobox Protein 1 as a key mesenchymal transcription factor in pulmonary fibrosis [ Elife, 2023, 12e79840]	PubMed: 37261432
Identification of Paired-related Homeobox Protein 1 as a key mesenchymal transcription factor in pulmonary fibrosis [ Elife, 2023, 12e79840]	PubMed: 37261432
Differences in Treatment Response in Bronchial Epithelial Cells from Idiopathic Pulmonary Fibrosis (IPF) Patients: A First Step towards Personalized Medicine [ Antioxidants (Basel), 2023, 12(2)443]	PubMed: 36830000

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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