Name: Niraparib (MK-4827)
Brand: Selleck Chemicals
SKU: S2741
Rating: 5 (116 reviews)

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Controllo Qualità (Quality Control)

Lotto: Purezza: 99.99%

99.99

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

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

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dell'attività	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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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare	320.39	Formula	C₁₉H₂₀N₄O	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	1038915-60-4	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 64 mg/mL (199.75 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 64 mg/mL

Water : 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.
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

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	PARP2 (Cell-free assay) 2.1 nM PARP1 (Cell-free assay) 3.8 nM
In vitro	In un saggio su cellule intere, Niraparib (MK-4827) ha inibito l'attività di PARP con un EC50 = 4 nM e ha inibito la proliferazione delle cellule tumorali con BRCA-1 e BRCA-2 mutati con un CC50 nell'intervallo 10-100 nM. È stato dimostrato essere un potente e selettivo inibitore di PARP-1 e PARP-2 con IC50=3,8 e 2,1 nM, rispettivamente. Inoltre, questo composto ha mostrato una selettività di almeno 100 volte superiore rispetto a PARP-3, V-PARP e tankyrase-1, con IC50 = 1300, 330 e 570 nM, rispettivamente. Oltre a inibire la crescita delle cellule HeLa prive di BRCA-1 a causa del silenziamento mediante interferenza dell'RNA, è in grado di inibire la proliferazione delle linee cellulari tumorali che portano mutazioni naturali di BRCA-1 o BRCA-2. Nelle cellule di adenocarcinoma della ghiandola mammaria umana MDA-MB-436 che portano mutazioni di BRCA-1, ha mostrato un CC50 = 18 nM, mentre nelle cellule di adenocarcinoma pancreatico umano CAPAN-1, che sono mutanti BRCA-2, ha mostrato un CC50 = 90 nM. Al contrario, le normali cellule epiteliali prostatiche e mammarie umane sono resistenti a MK-4827, mostrando effetti antiproliferativi nell'intervallo micromolare, dimostrando così l'altissima citotossicità selettiva di questi inibitori di PARP nelle cellule tumorali mutanti BRCA-1 e -2 rispetto al tessuto circostante.
In vivo	Niraparib (MK-4827), un nuovo inibitore di PARP-1 e PARP-2 biodisponibile per via orale, ha fortemente potenziato l'effetto delle radiazioni su una varietà di xenotrapianti tumorali umani, sia p53 wild type che p53 mutante. È stato ben tollerato in vivo e ha dimostrato efficacia come agente singolo in un modello di xenotrapianto di cancro deficiente in BRCA-1.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/22127459/ [2] https://pubmed.ncbi.nlm.nih.gov/19873981/

Applicazioni (Applications)

Metodi	Biomarcatori	Immagini	PMID
Western blot	c-PARP /c-caspase 3 / γ-H2AX		29158830
Immunofluorescence	Rad51 / Geminin		27614696

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
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

Domande Frequenti (Frequently Asked Questions)

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

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

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 (MK-4827) PARP Inibitore

Struttura chimica

Peso molecolare: 320.39

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)

Domande Frequenti (Frequently Asked Questions)

Niraparib (MK-4827) PARP Inibitore

Struttura chimica

Peso molecolare: 320.39

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)

Domande Frequenti (Frequently Asked Questions)

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