Name: BMS-777607
Brand: Selleck Chemicals
SKU: S1561
Rating: 5 (63 reviews)

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Contrôle Qualité (Quality Control)

Lot : Pureté : 99.64%

99.64

Cibles apparentées	EGFR VEGFR FGFR PDGFR Src MEK CSF-1R HER2 FLT3 c-Kit
Autre c-Met Inhibiteurs	Tepotinib (EMD-1214063) Dihexa SGX-523 PHA-665752 Foretinib (GSK1363089, XL880) SU11274 JNJ-38877605 Tivantinib PF-04217903 Savolitinib (AZD6094)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires	Type d'essai	Concentration	Temps d'incubation	Formulation	Description de l'activité	PMID
PC-3	Function assay	0.1 μM		DMSO	exhibits inhibitory effect on HGF-induced cell scattering	20515943
DU145	Function assay	0.1 μM		DMSO	exhibits inhibitory effect on HGF-induced cell scattering	20515943
PC-3	Function assay	0.01 μM		DMSO	suppresses HGF-induced cell migration	20515943
DU145	Function assay	0.01 μM		DMSO	suppresses HGF-induced cell migration	20515943
PC-3	Function assay	0.1 μM		DMSO	impairs HGF-mediated cell invasion	20515943
DU145	Function assay	0.1 μM		DMSO	impairs HGF-mediated cell invasion	20515943
PC-3	Growth inhibitory assay	~10 μM		DMSO	reduces cell proliferation	20515943
KHT	Kinase assay			DMSO	blocks the c-Met signaling pathway with IC50 of 10 nM	22286523
KHT	Function assay	~1 μM		DMSO	prevents spontaneous KHT cell scattering with IC50 of 0.1-0.5 μM	22286523
KHT	Function assay	~0.5 μM		DMSO	inhibits cell migration	22286523
KHT	Function assay	~0.5 μM		DMSO	inhibits cell invasion	22286523
KHT	Growth inhibitory assay	~10 μM		DMSO	inhibits KHT cell proliferation	22286523
T-47D	Growth inhibitory assay	~5 μM		DMSO	inhibits cell proliferation	23468529
ZR-75-1	Growth inhibitory assay	~5 μM		DMSO	inhibits cell proliferation	23468529
T-47D	Function assay	10 μM		DMSO	Induces polyploidy by 86 %	23468529
ZR-75-1	Function assay	10 μM		DMSO	Induces polyploidy by 88%	23468529
T-47D	Function assay	10 μM		DMSO	inhibits AURK-B function and induces its protein degradation	23468529
CHRF	Function assay	10 μM		DMSO	inhibits cell division	25304900
HPDE	Function assay	10 μM		DMSO	blocks constitutive activation and decreased AKT signaling	26477314
U118MG	Kinase assay	~3 μM		DMSO	blocks AXL phosphorylation	26848524
SF126	Kinase assay	~3 μM		DMSO	blocks AXL phosphorylation	26848524
U118MG	Cytoxicity assay	12.5 μM		DMSO	decreases glioma cell viability	26848524
SF126	Cytoxicity assay	12.5 μM		DMSO	decreases glioma cell viability	26848524
U118MG	Apoptosis assay	12.5 μM		DMSO	induces glioma cell apoptosis	26848524
SF126	Apoptosis assay	12.5 μM		DMSO	induces glioma cell apoptosis	26848524
U118MG	Function assay	12.5 μM		DMSO	blocks glioma cell migration and invasive growth pattern	26848524
SF126	Function assay	12.5 μM		DMSO	blocks glioma cell migration and invasive growth pattern	26848524
GTL16	Function assay		30 mins		Inhibition of Met phosphorylation in human GTL16 cells after 30 mins, IC50 = 0.02 μM.	19260711
GTL16	Antiproliferative assay		72 hrs		Antiproliferative activity against Met-dependent human GTL16 cells after 72 hrs by MTS assay, IC50 = 0.1 μM.	19260711
NCI-H1993	Antiproliferative assay		72 hrs		Antiproliferative activity against Met-dependent human NCI-H1993 cells after 72 hrs by MTS assay, IC50 = 0.15 μM.	19260711
U87	Antiproliferative assay		72 hrs		Antiproliferative activity against Met-driven human U87 cells after 72 hrs by MTS assay, IC50 = 0.16 μM.	19260711
BAF3	Cytotoxicity assay		72 hrs		Cytotoxicity against mouse BAF3 cells expressing TPR-Met assessed as growth inhibition after 72 hrs, IC50 = 0.1884 μM.	24792774
DU145	Antiinvasive assay		1 hr		Antiinvasive activity in human DU145 cells assessed as inhibition of HGF-induced cell motility preincubated for 1 hr before HGF treatment measured after 24 hrs by cell scattering assay, IC50 = 0.2 μM.	24900830
MKN45	Cytotoxicity assay		72 hrs		Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs, IC50 = 0.2858 μM.	24792774
NCI-H1993	Cytotoxicity assay		48 hrs		Cytotoxicity against human NCI-H1993 cells after 48 hrs by MTT assay, IC50 = 1.108 μM.	24900830
GTL16	Function assay	6.25 mg/kg			Cmax in human GTL16 cells xenografted athymic mouse at 6.25 mg/kg, po, Cmax = 4.5 μM.	19260711
GTL16	Function assay	50 mg/kg			Cmax in human GTL16 cells xenografted athymic mouse at 50 mg/kg, po, Cmax = 43.7 μM.	19260711
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC 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
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 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
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 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
MGHU3	Antiproliferative assay		72 hrs		Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay	30309671
RT112	Antiproliferative assay		72 hrs		Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay	30309671
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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire	512.89	Formule	C₂₅H₁₉ClF₂N₄O₄	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1025720-94-8	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	BMS 817378			Smiles	CCOC1=C(C(=O)N(C=C1)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C(=NC=C4)N)Cl)F

Solubilité (Solubility)

In vitro
Lot:

DMSO : 100 mg/mL (194.97 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
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.
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	4%DMSO 1 45%PEG300 2 5%Tween80 3 46%ddH2O Validé par les laboratoires Selleck. Si vous avez besoin d'ajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	5.000mg/ml (9.75mM)	Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 450 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 460 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre d'animaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter d'abord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Caractéristiques	A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.
Targets/IC₅₀/Ki	Axl (Cell-free assay) 1.1 nM RON (Cell-free assay) 1.8 nM Met (Cell-free assay) 3.9 nM Tyro3 (Cell-free assay) 4.3 nM Mer (Cell-free assay) 14 nM FLT3 (Cell-free assay) 16 nM Aurora B (Cell-free assay) 78 nM
In vitro	BMS-777607 is a selective ATP-competitive Met kinase inhibitor which potently blocks the autophosphorylation of c-Met with IC50 of 20 nM in GTL-16 cell lysates, and demonstrates selective inhibition of proliferation in Met-driven tumor cell lines, such as GTL-16 cell line, H1993 and U87. This compound inhibits hepatocyte growth factor (HGF)-triggered c-Met autophosphorylation with IC50 of <1 nM in PC-3 and DU145 prostate cancer cells. This compound has little effect on tumor cell growth, but exhibits inhibitory effect on HGF-induced cell scattering in PC-3 and DU145 cells, with almost complete inhibition at 0.5 μM. It also suppresses stimulated cell migration and invasion in a dose-dependent fashion (IC50 < 0.1 μM) in both cell lines. Application of this compound (~10 μM) to the highly metastatic murine KHT cells for 2 hours potently eliminates basal levels of autophosphorylated c-Met with IC50 of 10 nM without affecting the total c-Met, leading to dose-dependent inhibition of phosphorylation of downstream signaling molecules including ERK, Akt, p70S6K and S6. Treatment with this compound (~1 μM) for 24 hours potently inhibits the KHT cell scatter, motility and invasion at doses in the nanomolar range which consists with MET gene knockdown, and modestly affects cell proliferation and colony formation.
Essai kinase	Essai de la kinase Met
Essai kinase	La réaction de la kinase consiste en du GST-Met exprimé par baculovirus, 3 μg de poly(Glu/Tyr), 0,12 μCi de ³³P γ-ATP, 1 μM d'ATP dans 30 μL de tampon de kinase (20 mM Tris-Cl, 5 mM MnCl2, 0,1 mg/mL BSA, 0,5 mM DTT). Les réactions sont incubées pendant 1 heure à 30 °C et arrêtées par l'ajout d'acide trichloroacétique froid (TCA) à une concentration finale de 8 %. Les précipités de TCA sont recueillis sur des plaques unifiltres GF/C à l'aide d'un "Filtermate universal harvester", et les filtres sont quantifiés à l'aide d'un compteur à scintillation liquide TopCount 96 puits. Des courbes dose-réponse sont générées pour déterminer la concentration requise pour inhiber 50 % de la phosphorylation du substrat (IC50). Ce composé est dissous à 10 mM dans du DMSO et évalué à 10 concentrations, en double.
In vivo	Oral administration of BMS 777607 (6.25-50 mg/kg) significantly reduces tumor volumes of the GTL-16 human tumor xenografts in athymic mice with no observed toxicity. Administration of this compound (25 mg/kg/day) decreases the number of KHT lung tumor nodules (28.3%), improves the morphological hemorrhage, and significantly impairs the metastatic phenotype in the 6-8 week-old female C3H/HeJ mice injected with rodent fibrosarcoma KHT cells without apparent systemic toxicity compared to the control treatment. A low dose of this chemical (10 mg/kg) also offers a mild but not significant inhibition of lung nodule formation compared to the vehicle control.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/19260711/ [2] https://pubmed.ncbi.nlm.nih.gov/20515943/ [3] https://pubmed.ncbi.nlm.nih.gov/22286523/ [4] https://pubmed.ncbi.nlm.nih.gov/18690676/

Applications (Applications)

Méthodes	Biomarqueurs	Images	PMID
Western blot	p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6 p53 / p21 / Survivin / p-Rb / Rb		22639908
Immunofluorescence	α-tubulin / survivin		24444656

Informations sur l'essai clinique (Clinical Trial Information)

(données du https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Promoteur/Collaborateurs	Date de début	Phases
NCT01721148	Completed	Malignant Solid Tumour	ASLAN Pharmaceuticals	October 2012	Phase 1
NCT00605618	Completed	Advanced Solid Tumors	Bristol-Myers Squibb	March 2008	Phase 1\|Phase 2

Foire aux questions (Frequently Asked Questions)

Question 1:
What formulation can we use to dissolve it for mice in vivo study?

Réponse :
S1561 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30 mg/ml is a suspension. It is fine for oral gavage. If you are going to use it for injection, please try the following vehicle: 4% DMSO+30% PEG 300+ddH2O. This compound can be dissolved in it at 5 mg/ml as a clear solution.

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):

BMS-777607 c-Met Inhibiteur

Poids moléculaire: 512.89

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

Informations sur l'essai clinique (Clinical Trial Information)

Foire aux questions (Frequently Asked Questions)

BMS-777607 c-Met Inhibiteur

Poids moléculaire: 512.89

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail (Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

Informations sur l'essai clinique (Clinical Trial Information)

Foire aux questions (Frequently Asked Questions)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)