Name: Niraparib tosylate
Brand: Selleck Chemicals
SKU: S7625
Rating: 5 (42 reviews)

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Contrôle Qualité

Lot : Pureté : 99.99%

99.99

Cibles apparentées	HDAC ATM/ATR DNA-PK WRN DNA/RNA Synthesis Topoisomerase PPAR Sirtuin Casein Kinase eIF
Autre PARP Inhibiteurs	XAV-939 AZD5305 (Saruparib) Veliparib (ABT-888) PJ34 HCl AG-14361 Iniparib (BSI-201) G007-LK Pamiparib UPF 1069 A-966492

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
HeLa	Function assay			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC50 = 0.004 μM.	19873981
MDA-MB-436	Antiproliferative assay		6 days	Antiproliferative activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant after 6 days by cell titer-blue assay, CC50 = 0.018 μM.	19873981
HeLa	Antiproliferative assay		7 days	Antiproliferative activity against BRCA1 deficient human HeLa cells after 7 days by cell titer-blue assay, CC50 = 0.033 μM.	19873981
HeLa	Function assay			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC90 = 0.045 μM.	19873981
Capan1	Antiproliferative assay		13 days	Antiproliferative activity against human Capan1 cells expressing BRCA2 6174delT mutation and loss of wild-type allele after 13 days by cell titer-blue assay, CC50 = 0.09 μM.	19873981
HeLa	Antiproliferative assay		7 days	Antiproliferative activity against human HeLa cells expressing wild type BRCA1 after 7 days by cell titer-blue assay, CC50 = 0.86 μM.	19873981
MDA-MB-436	Antitumor assay	50 mg/kg	33 days	Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 50 mg/kg, po bid for 33 days	19873981
MDA-MB-436	Antitumor assay	100 mg/kg	33 days	Antitumor activity against human MDA-MB-436 cells expressing BRCA1 5396 + 1G>A mutant xenografted in CD1 mouse assessed as tumor regression at 100 mg/kg, po qd for 33 days	19873981
Jurkat	Function assay		96 hrs	Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay in presence of 100 uM of temozolomide, EC50 = 0.2 μM.	23850199
Jurkat	Function assay		96 hrs	Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay, EC50 = 31 μM.	23850199
CAPAN-1	Function assay			Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.0035 μM.	25761096
HeLa	Function assay			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, EC50 = 0.004 μM.	25761096
A2780	Function assay			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.004 μM.	25761096
A549	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human A549 cells transfected with BRCA2 shRNA assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.011 μM.	25761096
MDA-MB-436	Cytotoxicity assay			Cytotoxicity against human MDA-MB-436 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation, CC50 = 0.018 μM.	25761096
SUM1315MO2	Cytotoxicity assay		12 days	Cytotoxicity against human SUM1315MO2 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 12 days by CellTiter-Blue assay, CC50 = 0.02 μM.	25761096
DoTc2-4510	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human DoTc2-4510 cells carrying BRCA2 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.023 μM.	25761096
SUM149PT	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human SUM149PT cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.024 μM.	25761096
HeLa	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human HeLa cells transfected with BRCA1 shRNA assessed as reduction of cell viability after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.034 μM.	25761096
HeLa	Function assay			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.046 μM.	25761096
CAPAN-1	Function assay			Inhibition of PARP in BRCA2-deficient human CAPAN-1 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.05 μM.	25761096
A2780	Function assay			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.052 μM.	25761096
UWB1.289	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human UWB1.289 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.056 μM.	25761096
Capan1	Cytotoxicity assay			Cytotoxicity against BRCA2-deficient human Capan1 cells, CC50 = 0.09 μM.	25761096
HeLa	Cytotoxicity assay		5 to 7 days	Cytotoxicity against wild type human HeLa cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.852 μM.	25761096
UWB1.289	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human UWB1.289 cells expressing BRCA1 assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 0.975 μM.	25761096
A549	Cytotoxicity assay		5 to 7 days	Cytotoxicity against wild type human A549 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 1.76 μM.	25761096
BT20	Cytotoxicity assay		5 to 7 days	Cytotoxicity against human BT20 cells assessed as inhibition of cell proliferation after 5 to 7 days by CellTiter-Blue assay, CC50 = 2.2 μM.	25761096
MDA-MB-436	Antitumor assay	80 mg/kg	1 to 2 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 80 mg/kg, po qd for 1 to 2 weeks	25761096
MDA-MB-436	Antitumor assay	80 mg/kg	4 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as complete and sustained tumor regression at 80 mg/kg, po qd for 4 weeks	25761096
MDA-MB-436	Antitumor assay	50 mg/kg		Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor growth inhibition at 50 mg/kg, po administered daily	25761096
MDA-MB-436	Antitumor assay	80 mg/kg	3 weeks	Antitumor activity against human MDA-MB-436 cells harboring BRCA1 mutant xenografted in immunocompromised mouse assessed as tumor shrinkage at 80 mg/kg, po qd for 3 weeks	25761096
Capan1	Cytotoxicity assay			Cytotoxicity against BRCA2-deficient human Capan1 cells, EC50 = 0.65 μM.	26652717
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
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 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
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
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
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Informations chimiques, stockage et stabilité

Poids moléculaire	492.59	Formule	C₁₉H₂₀N₄O.C₇H₈O₃S	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	1038915-73-9	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	MK 4827 tosylate			Smiles	CC1=CC=C(C=C1)S(=O)(=O)O.C1CC(CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)N

Solubilité

In vitro
Lot:

DMSO : 99 mg/mL (200.97 mM)
(Le DMSO contaminé par lhumidité 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	4.950mg/ml (10.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 99 mg/ml clarified DMSO stock solution to 400 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 500 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.

Calculateur de formulation in vivo (Solution claire)

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

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

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny 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 dabord 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 dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue, lors de lajout précédent, est une solution claire avant de procéder à lajout 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 daction

Targets/IC₅₀/Ki	PARP2 (Cell-free assay) 2.1 nM PARP1 (Cell-free assay) 3.8 nM
In vitro	Des concentrations micromolaires de niraparib radiosensibilisent les lignées cellulaires tumorales dérivées des cancers du poumon, du sein et de la prostate, indépendamment de leur statut p53, mais pas les lignées cellulaires dérivées de tissus normaux. Le niraparib sensibilise également les cellules tumorales au H2O2 et convertit les cassures simple brin (SSB) induites par le H2O2 en DSB pendant la réplication de l'ADN.
In vivo	Le MK-4827 améliore fortement l'effet de la radiothérapie sur une variété de xénogreffes tumorales humaines, qu'elles soient de type sauvage p53 ou mutantes p53. Le MK-4827 réduit les niveaux de PAR dans les tumeurs 1 h après l'administration, effet qui persiste jusqu'à 24 h. Le traitement in vivo avec le MK-4827 et la radiothérapie a prolongé la survie (p<0,01) par rapport aux monothérapies. La supériorité in vivo du MK-4827 plus radiothérapie est également documentée par des augmentations significatives de la caspase-3 clivée et du γ-H2AX dans les tumeurs du groupe combiné par rapport aux cohortes en monothérapie.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/22127459/ [2] https://pubmed.ncbi.nlm.nih.gov/22158865/ [3] https://pubmed.ncbi.nlm.nih.gov/19873981/ [4] https://pubmed.ncbi.nlm.nih.gov/23482742/ [5] https://pubmed.ncbi.nlm.nih.gov/24970803/

Applications

Méthodes	Biomarqueurs	Images	PMID
Western blot	c-PARP /c-caspase 3 / γ-H2AX		29158830
Immunofluorescence	Rad51 / Geminin		27614696

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

Si vous avez dautres questions, veuillez laisser un message.

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):

Niraparib tosylate PARP inhibiteur

Structure chimique

Poids moléculaire: 492.59