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Veliparib (ABT-888) PARP Remmer

Name: Veliparib (ABT-888)
Brand: Selleck Chemicals
SKU: S1004
Rating: 5 (257 reviews)

Cat.nr.: S1004

Veliparib (ABT-888, NSC 737664) is een krachtige remmer van PARP1 en PARP2 met een K_i van respectievelijk 5,2 nM en 2,9 nM in celvrije assays. Deze verbinding is inactief voor SIRT2 en verhoogt autophagy en apoptosis. Fase 3.

Veliparib (ABT-888) PARP Remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 244.29

Spring naar

Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.94%

99.94

Gerelateerde doelwitten	HDAC ATM/ATR DNA-PK WRN DNA/RNA Synthesis Topoisomerase PPAR Sirtuin Casein Kinase eIF
Overig PARP Inhibitoren	XAV-939 AZD5305 (Saruparib) PJ34 HCl AG-14361 Iniparib (BSI-201) G007-LK A-966492 UPF 1069 Pamiparib ME0328

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
A4-Fuk	Growth Inhibition Assay				IC50=43.5691 μM	SANGER
JVM-2	Growth Inhibition Assay				IC50=42.9207 μM	SANGER
MOLT-4	Growth Inhibition Assay				IC50=42.2538 μM	SANGER
KARPAS-45	Growth Inhibition Assay				IC50=41.4818 μM	SANGER
HCC1187	Growth Inhibition Assay				IC50=41.2771 μM	SANGER
NB14	Growth Inhibition Assay				IC50=40.7031 μM	SANGER
SW982	Growth Inhibition Assay				IC50=38.0998 μM	SANGER
IGROV-1	Growth Inhibition Assay				IC50=39.3304 μM	SANGER
CAL-54	Growth Inhibition Assay				IC50=37.966 μM	SANGER
T47D	Growth Inhibition Assay				IC50=37.7018 μM	SANGER
H4	Growth Inhibition Assay				IC50=37.567 μM	SANGER
LAMA-84	Growth Inhibition Assay				IC50=36.7345 μM	SANGER
MV-4-11	Growth Inhibition Assay				IC50=35.8499 μM	SANGER
KG-1	Growth Inhibition Assay				IC50=33.6001 μM	SANGER
JVM-3	Growth Inhibition Assay				IC50=35.5868 μM	SANGER
MFE-280	Growth Inhibition Assay				IC50=33.3889 μM	SANGER
KU812	Growth Inhibition Assay				IC50=32.3642 μM	SANGER
COLO-684	Growth Inhibition Assay				IC50=33.3599 μM	SANGER
A2780	Growth Inhibition Assay				IC50=30.7457 μM	SANGER
RS4-11	Growth Inhibition Assay				IC50=30.4241 μM	SANGER
EM-2	Growth Inhibition Assay				IC50=29.4901 μM	SANGER
L-363	Growth Inhibition Assay				IC50=29.4798 μM	SANGER
MOLT-13	Growth Inhibition Assay				IC50=29.3814 μM	SANGER
EW-13	Growth Inhibition Assay				IC50=29.3814 μM	SANGER
LU-139	Growth Inhibition Assay				IC50=29.3748 μM	SANGER
697	Growth Inhibition Assay				IC50=29.0235 μM	SANGER
LB771	Growth Inhibition Assay				IC50=28.8373 μM	SANGER
SK-MEL-1	Growth Inhibition Assay				IC50=12.4663 μM	SANGER
CAL-33	Growth Inhibition Assay				IC50=10.434 μM	SANGER
HAL-01	Growth Inhibition Assay				IC50=9.8862 μM	SANGER
KASUMI-1	Growth Inhibition Assay				IC50=8.89266 μM	SANGER
NCI-H720	Growth Inhibition Assay				IC50=8.43603 μM	SANGER
C41	Kinase Assay		30 min		Inhibition of PARP1 with EC50 of 0.002 μM	19888760
Jurkat	Kinase Assay		96 h	DMSO	Inhibition of PARP1 assessed as reduction of cell viability with EC50 of 3 μM	23850199
Capan1	Growth Inhibition Assay		72 h	DMSO	Antiproliferative activity against BRCA2 gene mutated human Capan1 cells with IC50 of 39.7 μM	24398383
ML-1	Apoptotic Assay	2.5 μM	24 h	DMSO	Synergistically enhances TRAIL-induced apoptosis in ML-1 cells	24895135
HCT-116	Kinase Assay	0.5 μM	24 h		PARP activity decreases	23054213
UM-SCC1	Cytotoxic Assay	10 μM	24 h		Reduces the cell viability	21912620
FaDu	Cytotoxic Assay	10 μM	24 h		Reduces the cell viability	21912620
LoVo	Function assay		30 mins		Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay, EC50 = 0.00594 μM.	26652717
LoVo	Function assay		30 mins		Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay, EC50 = 0.00594 μM.	26652717
LoVo	Function assay		30 mins		Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay, EC50 = 0.00594 μM.	26652717
VC8	Cytotoxicity assay		3 days		Cytotoxicity against Chinese hamster VC8 cells harboring BRCA2 deficient after 3 days by CCK8 assay, CC50 = 2.344 μM.	29335205
LoVo	Cytotoxicity assay	0.4 uM	5 days		Potentiation of -induced cytotoxicity in human LoVo cells assessed as GI50 at 0.4 uM after 5 days by Celltiter-Glo assay, GI50 = 6.203 μM.	26652717
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SK-N-SH cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
T98G	Growth Inhibition Assay				IC50=44.8517 μM	SANGER
BALL-1	Growth Inhibition Assay				IC50=43.9532 μM	SANGER
MDA-MB-361	Growth Inhibition Assay				IC50=43.8414 μM	SANGER
SBC-1	Growth Inhibition Assay				IC50=41.3063 μM	SANGER
MOLT-16	Growth Inhibition Assay				IC50=36.952 μM	SANGER
BEN	Growth Inhibition Assay				IC50=27.9566 μM	SANGER
HCC70	Growth Inhibition Assay				IC50=27.7246 μM	SANGER
NCI-H1693	Growth Inhibition Assay				IC50=27.2898 μM	SANGER
HLE	Growth Inhibition Assay				IC50=27.054 μM	SANGER
NCI-H2029	Growth Inhibition Assay				IC50=26.4238 μM	SANGER
CTV-1	Growth Inhibition Assay				IC50=25.8969 μM	SANGER
TGBC11TKB	Growth Inhibition Assay				IC50=25.6863 μM	SANGER
HCC1937	Growth Inhibition Assay				IC50=24.746 μM	SANGER
MHH-NB-11	Growth Inhibition Assay				IC50=23.1363 μM	SANGER
A388	Growth Inhibition Assay				IC50=21.9091 μM	SANGER
ECC10	Growth Inhibition Assay				IC50=20.7455 μM	SANGER
Daoy	Growth Inhibition Assay				IC50=19.5649 μM	SANGER
KYSE-150	Growth Inhibition Assay				IC50=18.9986 μM	SANGER
NKM-1	Growth Inhibition Assay				IC50=18.5119 μM	SANGER
H9	Growth Inhibition Assay				IC50=18.2833 μM	SANGER
COLO-668	Growth Inhibition Assay				IC50=17.6294 μM	SANGER
GP5d	Growth Inhibition Assay				IC50=17.053 μM	SANGER
DEL	Growth Inhibition Assay				IC50=16.6717 μM	SANGER
ChaGo-K-1	Growth Inhibition Assay				IC50=16.5325 μM	SANGER
RPMI-8226	Growth Inhibition Assay				IC50=16.2042 μM	SANGER
OS-RC-2	Growth Inhibition Assay				IC50=15.9589 μM	SANGER
EW-3	Growth Inhibition Assay				IC50=14.5565 μM	SANGER
DU-145	Growth Inhibition Assay				IC50=13.9053 μM	SANGER
MN-60	Growth Inhibition Assay				IC50=13.5389 μM	SANGER
SK-NEP-1	Growth Inhibition Assay				IC50=13.166 μM	SANGER
HEC-1	Growth Inhibition Assay				IC50=12.9196 μM	SANGER
KY821	Growth Inhibition Assay				IC50=12.485 μM	SANGER
Ramos-2G6-4C10	Growth Inhibition Assay				IC50=12.4752 μM	SANGER
DT40	Cytotoxic Assay		72 h	DMSO	Cytotoxicity against chicken BRCA2-deficient DT40 cells	24922587
PC-3	Growth Inhibition Assay	10 μM			Induces a significant inhibition in colony formation	21571912
C41	Function assay				Inhibition of PARP1 in human C41 cells, EC50 = 0.002 μM.	19143569
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
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
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells	29435139
EoL-1-cell	Growth Inhibition Assay				IC50=1.0798 μM	SANGER
NCI-SNU-5	Growth Inhibition Assay				IC50=3.12841 μM	SANGER
BV-173	Growth Inhibition Assay				IC50=5.45409 μM	SANGER
HCC1806	Growth Inhibition Assay				IC50=5.75173 μM	SANGER
COLO-680	Growth Inhibition Assay				IC50=6.21406 μM	SANGER
HCC2218	Growth Inhibition Assay				IC50=7.79704 μM	SANGER
SK-MEL-24	Growth Inhibition Assay				IC50=7.81924 μM	SANGER
Mo-T	Growth Inhibition Assay				IC50=45.6389 μM	SANGER
MHH-PREB-1	Growth Inhibition Assay				IC50=45.7585 μM	SANGER
ALL-PO	Growth Inhibition Assay				IC50=47.3791 μM	SANGER
NCI-H510A	Growth Inhibition Assay				IC50=47.9034 μM	SANGER
ML-2	Growth Inhibition Assay				IC50=49.7856 μM	SANGER
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	244.29	Formule	C₁₃H₁₆N₄O	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	912444-00-9	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	NSC 737664			Smiles	CC1(CCCN1)C2=NC3=C(C=CC=C3N2)C(=O)N

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 49 mg/mL (200.58 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 50 mg/mL (204.67 mM) Verwarmd met een waterbad van 60°C; Geultrasoneerd;
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 2 mg/mL (超声加热)

Water : Insoluble

DMSO : 50 mg/mL (204.67 mM) Verwarmd met een waterbad van 60°C; Geultrasoneerd;
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 2 mg/mL (超声加热)

Water : 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.
Clear solution	5%DMSO 1 40%PEG 300 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.	5.000mg/ml (20.47mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL 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	0.5% methylcellulose 1 0.2% Tween 80 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	5.000mg/ml (20.47mM)	Taking the 1 mL working solution as an example, take 5 mg of this product and add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results.

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 (Mechanism of Action)

Kenmerken	Increases the efficacy of common cancer therapies such as radiation and alkylating agents.
Targets/IC₅₀/Ki	PARP2 (Cell-free assay) 2.9 nM(Ki) PARP1 (Cell-free assay) 5.2 nM(Ki)
In vitro	Veliparib (ABT-888) is inactive to SIRT2 (>5 μM). It inhibits the PARP activity with EC50 of 2 nM in C41 cells. This compound could decrease the PAR levels in both irradiated and nonirradiated H460 cells. It also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. When combined with radiation, it increases apoptosis and autophagy in H460 cells. It also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. At 10 μM, it suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. It shows effective radiosensitivity in oxic H1299 cells. Furthermore, it could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1.
Kinase Assay	In vitro PARP-assays
Kinase Assay	PARP-assays voor Veliparib (ABT-888) worden uitgevoerd in een buffer die 50 mM Tris (pH 8.0), 1 mM DTT, 1,5 μM [³H]NAD⁺ (1,6 μCi/mmol), 200 nM gebiotinyleerd histone H1, 200 nM slDNA en 1 nM PARP-1 of 4 nM PARP-2 enzym bevat. Reacties worden beëindigd met 1,5 mM benzamide, overgebracht naar streptavidin Flash-platen en geteld met behulp van een TopCount microplaat scintillatieteller.
In vivo	Veliparib (ABT-888) has an oral bioavailability of 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. This compound (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, it decreases the tumor vessel formation. It reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models and the suppression could be maintained over time.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/17473206/ [2] https://pubmed.ncbi.nlm.nih.gov/19143569/ [3] https://pubmed.ncbi.nlm.nih.gov/17505006/ [4] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766769/ [11] null [12] https://pubmed.ncbi.nlm.nih.gov/17473206/ [13] https://pubmed.ncbi.nlm.nih.gov/22678161/

Toepassingen (Applications)

Methoden	Biomarkers	PMID
Western blot	p-STAT3 / STAT3 / p-AKT(S473) / p-AKT(T308) / p-ERK / p-p38	22678161
Immunofluorescence	HuR BRCA1	28687616
Growth inhibition assay	Cell viability (TNBC cell lines) Cell viability (melanoma cells)	27880910

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT03044795	Withdrawn	Cancer	University Medical Center Groningen\|AbbVie\|Dutch Cancer Society	November 2019	Phase 2
NCT02723864	Completed	Neoplasms	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	August 9 2017	Phase 1
NCT02483104	Completed	Ovarian Cancer	AbbVie	July 2015	Phase 1

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):

Veliparib (ABT-888) PARP Remmer

Molecuulgewicht: 244.29

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie over klinische proeven (Clinical Trial Information)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)