Name: Niraparib (MK-4827)
Brand: Selleck Chemicals
SKU: S2741
Rating: 5 (109 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 cells	Function assay			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC50=0.004 μM	19873981
A549 cells	Cytotoxicity assay		5-7 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 cells	Proliferation 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=18 nM	19873981
SUM1315MO2 cells	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 cells	Cytotoxicity assay		5-7 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 cells	Cytotoxicity assay		5-7 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
UWB1.289 cells	Cytotoxicity assay		5-7 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 cells	Cytotoxicity assay			Cytotoxicity against BRCA2-deficient human Capan1 cells, CC50=0.09 μM	25761096
Jurkat cells	Function assay			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
BT20 cells	Cytotoxicity assay		5-7 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
Antiproliferative assay	HeLa		7 days	Antiproliferative activity against BRCA1 deficient human HeLa cells after 7 days by cell titer-blue assay, CC50 = 0.033 μM.	19873981
Function assay	HeLa			Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation, EC90 = 0.045 μM.	19873981
Antiproliferative assay	Capan1		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
Antiproliferative assay	HeLa		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
Function assay	Jurkat		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
Function assay	CAPAN-1			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
Function assay	HeLa			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, EC50 = 0.004 μM.	25761096
Function assay	A2780			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC50 = 0.004 μM.	25761096
Cytotoxicity assay	MDA-MB-436			Cytotoxicity against human MDA-MB-436 cells carrying BRCA1 mutant assessed as inhibition of cell proliferation, CC50 = 0.018 μM.	25761096
Cytotoxicity assay	HeLa		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
Function assay	HeLa			Inhibition of PARP in human HeLa cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.046 μM.	25761096
Function assay	CAPAN-1			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
Function assay	A2780			Inhibition of PARP in human A2780 cells assessed as inhibition of hydrogen peroxide-induced PARylation by cell-based assay, IC90 = 0.052 μM.	25761096
Cytotoxicity assay	HeLa		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
Cytotoxicity assay	UWB1.289		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
Cytotoxicity assay	A549		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
Cytotoxicity assay	Capan1			Cytotoxicity against BRCA2-deficient human Capan1 cells, EC50 = 0.65 μM.	26652717
Antitumor assay	MDA-MB-436	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
Antitumor assay	MDA-MB-436	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
Antitumor assay	MDA-MB-436	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
Antitumor assay	MDA-MB-436	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
Antitumor assay	MDA-MB-436	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
Antitumor assay	MDA-MB-436	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
qHTS assay	TC32			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
qHTS assay	A673			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
qHTS assay	NB1643			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
qHTS assay	A673			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
qHTS assay	BT-37			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
qHTS assay	SK-N-MC			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
qHTS assay	NB-EBc1			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
qHTS assay	LAN-5			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
qHTS assay	SK-N-MC			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
qHTS assay	TC32			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	320.39	Formule	C₁₉H₂₀N₄O	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	1038915-60-4	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant

Solubilité

In vitro
Lot:

DMSO : 64 mg/mL (199.75 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 64 mg/mL

Water : 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 de vente pour des tests personnalisés.	2.500mg/ml (7.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 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 make it clear; 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.
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 de vente pour des tests personnalisés.	2.500mg/ml (7.80mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 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 make it clear; 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.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Entrez 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 : Entrez la formulation in vivo (Ceci nest que 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, ajouter ensuiteμL PEG300, mélanger et clarifier, ajouter ensuiteμL Tween 80, mélanger et clarifier, ajouter ensuite μL ddH₂O, mélanger et clarifier.

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

Remarque : 1. Assurez-vous 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 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	Dans un test sur cellules entières, Niraparib (MK-4827) a inhibé l'activité PARP avec une EC50 = 4 nM et a inhibé la prolifération des cellules cancéreuses avec des mutations BRCA-1 et BRCA-2 avec une CC50 dans la plage de 10-100 nM. Il s'est avéré être un inhibiteur puissant et sélectif de PARP-1 et PARP-2 avec une IC50 respective de 3,8 et 2,1 nM. De plus, ce composé a montré une sélectivité au moins 100 fois supérieure à celle de PARP-3, V-PARP et tankyrase-1, avec des IC50 respectives de 1300, 330 et 570 nM. En plus d'inhiber la croissance des cellules HeLa dépourvues de BRCA-1 en raison d'un silençage par interférence ARN, il est capable d'inhiber la prolifération des lignées cellulaires cancéreuses portant des mutations naturelles BRCA-1 ou BRCA-2. Dans les cellules d'adénocarcinome mammaire humain MDA-MB-436 portant des mutations BRCA-1, il a montré une CC50 = 18 nM, tandis que dans les cellules d'adénocarcinome pancréatique humain CAPAN-1, qui sont mutantes BRCA-2, il a montré une CC50 = 90 nM. En revanche, les cellules épithéliales prostatiques et mammaires humaines normales sont résistantes au MK-4827, montrant des effets antiprolifératifs dans la gamme micromolaire, démontrant ainsi la cytotoxicité sélective très élevée de ces inhibiteurs de PARP dans les cellules cancéreuses mutantes BRCA-1 et -2 par rapport aux tissus environnants.
In vivo	Niraparib (MK-4827), un nouvel inhibiteur de PARP-1 et PARP-2 biodisponible par voie orale, a fortement amélioré l'effet des radiations sur une variété de xénogreffes de tumeurs humaines, à la fois de type sauvage p53 et de type mutant p53. Il a été bien toléré in vivo et a démontré une efficacité en tant qu'agent unique dans un modèle de xénogreffe de cancer déficient en BRCA-1.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/22127459/ [2] https://pubmed.ncbi.nlm.nih.gov/19873981/

Applications

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

Informations sur lessai clinique

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

Numéro NCT	Recrutement	Conditions	Sponsor/Collaborateurs	Date de début	Phases
NCT05289648	Not yet recruiting	Endometrial Cancer\|Serous Adenocarcinoma\|Uterine Neoplasm	Sir Mortimer B. Davis - Jewish General Hospital	May 1 2024	Early Phase 1
NCT06077877	Recruiting	Neoplasms	GlaxoSmithKline	October 24 2023	Phase 1\|Phase 2
NCT05666349	Withdrawn	Recurrent Glioblastoma	University College London\|GlaxoSmithKline	October 13 2023	Phase 1

Support technique

Instructions de manipulation

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

Si vous avez dautres questions, veuillez laisser un message.

Questions fréquemment posées

Question 1:
How to reconstitute it for in vivo studies?

Réponse :
It can be orally administered using the formulation 1% CMC-Na (suspension).

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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 (MK-4827) PARP inhibiteur

Structure chimique

Poids moléculaire: 320.39