Name: BIBF 1120 (Nintedanib)
Brand: Selleck Chemicals
SKU: S1010
Rating: 5 (150 reviews)

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.98%

99.98

Target correlati	EGFR FGFR PDGFR c-Met Src MEK CSF-1R HER2 FLT3 c-Kit
Altro VEGFR Inibitori	SAR131675 SU 5402 Cediranib (AZD2171) Vatalanib (PTK787) 2HCl Anlotinib (AL3818) Dihydrochloride Linifanib (ABT-869) Apatinib (YN968D1) Apatinib (YN968D1) mesylate Ki8751 Semaxanib (SU5416)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dell'attività	PMID
SKOV3	Function Assay	5 µM	24 h	DMSO	induces a significant increase in the promoter activities of E-cad, CDH1, and CDH3	26061747
A549	Function Assay	2/5 μM	24 h	DMSO	has a general EMT reversal effect	26061747
T24	Function Assay	2/5 μM	24 h	DMSO	has a general EMT reversal effect	26061747
Mia-Paca2	Function Assay	2/5 μM	24 h	DMSO	has a general EMT reversal effect	26061747
A549	Function Assay	0.01–5 μM	24 h	DMSO	induces SFTPD mRNA expression dose dependently	25843005
A549	Function Assay	0.01–5 μM	72 h	DMSO	enhances SP-D protein expression in a dose-dependent manner at concentrations of up to 5 μM	25843005
A549	Function Assay	5 μM	0-1 h	DMSO	increases AP-1 activation after 30 min	25843005
Hep3B	Cell Viability Assay	0-20 μM	48 h		decreases cell viability dose dependently	24657398
HepG2	Cell Viability Assay	0-20 μM	48 h		decreases cell viability dose dependently	24657398
PLC5	Cell Viability Assay	0-20 μM	48 h		decreases cell viability dose dependently	24657398
HuH7	Cell Viability Assay	0-20 μM	48 h		decreases cell viability dose dependently	24657398
SK-Hep1	Cell Viability Assay	0-20 μM	48 h		decreases cell viability dose dependently	24657398
Hep3B	Apoptosis Assay	0-20 μM	48 h		induces cell apoptosis dose dependently	24657398
HepG2	Apoptosis Assay	0-20 μM	48 h		induces cell apoptosis dose dependently	24657398
PLC5	Apoptosis Assay	0-20 μM	48 h		induces cell apoptosis dose dependently	24657398
HuH7	Apoptosis Assay	0-20 μM	48 h		induces cell apoptosis dose dependently	24657398
SK-Hep1	Apoptosis Assay	0-20 μM	48 h		induces cell apoptosis dose dependently	24657398
H1703	Growth Inhibition Assay				IC50=0.05 μM	23729403
Sf9	Function assay		20 mins		Inhibition of mouse GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.013 μM.	18559524
Sf9	Function assay		20 mins		Inhibition of human GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.021 μM.	18559524
NIH3T3	Function assay	50 nM	1 hr		Inhibition of VEGFR2 transfected in mouse NIH3T3 cells at 50 nM incubated for 1 hr measured after 32 hrs washout followed by VEGF stimulation for 10 mins by Western blotting	18559524
HT-29	Antiproliferative assay		72 hrs		Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 4.9 μM.	28190652
SKOV3	Antiproliferative assay		72 hrs		Antiproliferative activity against human SKOV3 cells after 72 hrs by MTT assay, IC50 = 28.76 μM.	28190652
BL21 (DE3)	Function assay		30 mins		Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, Ki = 0.0056 μM.	28351607
BL21 (DE3)	Function assay		30 mins		Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, IC50 = 0.043 μM.	28351607
HT-29	Antiproliferative assay		72 hrs		Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.83 μM.	28826084
MCF7	Antiproliferative assay		72 hrs		Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 8.28 μM.	28826084
A549	Antiproliferative assay		72 hrs		Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 22.62 μM.	28826084
NIH/3T3	Function assay		42 hrs		Inhibition of PDGFR in mouse NIH/3T3 cells assessed as reduction in recombinant human PDGF-BB-induced cell proliferation after 42 hrs by cell titer 96 aqueous one solution based assay, IC50 = 0.085 μM.	29152045
Sf9	Function assay				Inhibition of human VEGFR2 expressed in Sf9 cells, IC50 = 0.005 μM.	19522465
NIH3T3	Function assay		1 hr		Inhibition of VEGF-stimulated human VEGFR2 phosphorylation expressed in mouse NIH3T3 cells pretreated for 1 hr measured 32 hrs after drug dose by immunoprecipitation based pulse-chase experiment	19522465
BRP	Apoptosis assay				Induction of apoptosis in BRP cells assessed as caspase-3 cleavage	19522465
BRP	Antiangiogenic assay				Antiangiogenic activity BRP cells assessed as inhibition of cell proliferation by [3H]thymidine incorporation assay	19522465
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
BT-37	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
OHS-50	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
Rh41	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	539.62	Formula	C₃₁H₃₃N₅O₄	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	656247-17-5	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	BIBF 1120, Intedanib			Smiles	CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 10 mg/mL (18.53 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 10 mg/mL (18.53 mM) Riscaldato con bagno d'acqua a 60°C; Sonicato;
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 2 mg/mL

Water : Insoluble

DMSO : 18 mg/mL (33.35 mM) Riscaldato con bagno d'acqua a 60°C; Sonicato;
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 2%Tween80 3 53%ddH2O Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	0.250mg/ml (0.46mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 530 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante l'esperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC₅₀/Ki	VEGFR2 (Cell-free assay) 13 nM VEGFR3 (Cell-free assay) 13 nM LCK (Cell-free assay) 16 nM FLT3 (Cell-free assay) 26 nM VEGFR1 (Cell-free assay) 34 nM FGFR2 (Cell-free assay) 37 nM PDGFRα (Cell-free assay) 59 nM PDGFRβ (Cell-free assay) 65 nM FGFR1 (Cell-free assay) 69 nM FGFR3 (Cell-free assay) 108 nM Src (Cell-free assay) 156 nM Lyn (Cell-free assay) 195 nM FGFR4 (Cell-free assay) 610 nM
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.
Saggio chinasico	Saggio chinasi VEGFR2
Saggio chinasico	Il dominio tirosina chinasico citoplasmatico di VEGFR2 (residui 797-1355 secondo la sequenza depositata nella banca dati SWISS-PROT P35968) viene clonato in pFastBac fuso a GST ed estratto. L'attività enzimatica viene saggiata in presenza o assenza di diluizioni seriali di BIBF1120 eseguite in DMSO al 25%. Ogni piastra per microtitolazione contiene controlli interni come il bianco, la reazione massima e il composto di riferimento storico. Tutte le incubazioni vengono condotte a temperatura ambiente su uno shaker rotante. 10 μL di ogni diluizione di BIBF1120 vengono aggiunti a 10 μL di chinasi diluita (0,8 μg/mL VEGFR2, 10 mM Tris pH 7,5, 2 mM EDTA e 2 mg/mL BSA) e preincubati per 1 ora. La reazione viene avviata aggiungendo 30 μL di miscela di substrato contenente 62,4 mM Tris pH 7,5, 2,7 mM DTT, 5,3 mM MnCl₂, 13,3 mM Mg-acetato, 0,42 mM ATP, 0,83 mg/mL Poly-Glu-Tyr(4:1) e 1,7 μg/mL Poly-Glu-Tyr(4:1)-biotina e incubata per 1 ora. La reazione viene arrestata aggiungendo 50 μL di 250 mM EDTA, 20 mM HEPES, pH 7,4. 90 μL della miscela di reazione vengono trasferiti su una piastra di streptavidina e incubati per 1-2 ore. Dopo tre lavaggi con PBS, viene aggiunto l'anticorpo marcato con EU, PY20 (diluizione raccomandata 1:2000 di 0,5 mg/mL di anticorpo marcato in tampone di saggio DELFIA). L'eccesso di anticorpo di rilevazione viene rimosso con tre lavaggi di tampone di lavaggio DELFIA. Quindi, 10 minuti prima della misurazione sul lettore multilabel, ogni pozzetto viene incubato con 100 μL di soluzione di potenziamento DELFIA.
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.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/18559524/ [2] # [3] https://pubmed.ncbi.nlm.nih.gov/19522465/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	p-EGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK Cyclin A / Cyclin D1 / Cyclin E / CDK2 / CDK4 / CDK6 p-SMAD3 / SMAD3 / p-p38 MAPK / p38 MAPK Fibronectin / Collagen 1a1		27581340
Immunofluorescence	Vimentin / E-cadherin		29934570

Informazioni sullo studio clinico (Clinical Trial Information)

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT06200714	Recruiting	Idiopathic Pulmonary Fibrosis\|Diarrhoea	Boehringer Ingelheim	April 30 2024	--
NCT05676112	Withdrawn	Pulmonary Fibrosis	Boehringer Ingelheim\|China-Japan Friendship Hospital	December 29 2023	--
NCT06070610	Completed	Healthy	Boehringer Ingelheim	November 8 2023	Phase 1
NCT05755308	Not yet recruiting	Idiopathic Pulmonary Fibrosis	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	October 2023	Not Applicable
NCT06071013	Not yet recruiting	Non-small Cell Lung Cancer\|EGFR Gene Mutation\|EGFR-TKI Resistant Mutation	China Medical University Hospital	September 28 2023	Phase 1\|Phase 2

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

BIBF 1120 (Nintedanib) PDGFR/VEGFR inhibitor

Struttura chimica

Peso molecolare: 539.62

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

BIBF 1120 (Nintedanib) PDGFR/VEGFR inhibitor

Struttura chimica

Peso molecolare: 539.62

Controllo Qualità (Quality Control)

Coltura cellulare, trattamento e concentrazione di lavoro (Cell Culture, Treatment & Working Concentration)

Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Solubilità (Solubility)

Calcolatore di Molarità

Calcolatore di formulazione in vivo (Soluzione chiara)

Meccanismo d'azione (Mechanism of Action)

Applicazioni (Applications)

Informazioni sullo studio clinico (Clinical Trial Information)

Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)