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

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Batch: Zuiverheid: 99.99%

99.99

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

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	492.59	Formule	C₁₉H₂₀N₄O.C₇H₈O₃S	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1038915-73-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	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

Oplosbaarheid

In vitro
Batch:

DMSO : 99 mg/mL (200.97 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	PARP2 (Cell-free assay) 2.1 nM PARP1 (Cell-free assay) 3.8 nM
In vitro	Micromolaire concentraties van niraparib radiosensibiliseren tumorzellijnen afgeleid van long-, borst- en prostaatkanker onafhankelijk van hun p53-status, maar niet cellijnen afgeleid van normale weefsels. Niraparib maakt tumorcellen ook gevoelig voor H2O2 en zet H2O2-geïnduceerde enkelstrengsbreuken (SSB's) om in DSB's tijdens DNA-replicatie.
In vivo	MK-4827 versterkt het effect van straling sterk op een verscheidenheid aan menselijke tumorxenografts, zowel p53 wild type als p53 mutant. MK-4827 vermindert PAR-niveaus in tumoren binnen 1 uur na toediening en dit effect hield tot 24 uur aan. In vivo behandeling met MK-4827 en straling verlengde de overleving (p<0,01) vergeleken met enkelvoudige modaliteiten. De in vivo superioriteit van MK-4827 plus straling wordt verder gedocumenteerd door significante verhogingen van gekliefd caspase-3 en γ-H2AX in tumoren van de combinatiegroep vergeleken met enkelvoudige modaliteitscohorten.
Referenties	[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/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	c-PARP /c-caspase 3 / γ-H2AX		29158830
Immunofluorescence	Rad51 / Geminin		27614696

Technische ondersteuning

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Niraparib tosylate PARP remmer

Chemische structuur

Molecuulgewicht: 492.59