Veliparib (ABT-888)

Catalog No.S1004

Veliparib (ABT-888) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Phase 3.

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Veliparib (ABT-888) Chemical Structure

Veliparib (ABT-888) Chemical Structure
Molecular Weight: 244.29

Validation & Quality Control

Cited by 38 publications:

9 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Veliparib (ABT-888) is available in the following compound libraries:

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  • PARP Inhibitor in Clinical Trial

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  • Newest PARP Inhibitor

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Product Information

  • Compare PARP Inhibitors
    Compare PARP Products
  • Research Area
  • Veliparib (ABT-888) Mechanism
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Veliparib (ABT-888) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Phase 3.
Targets PARP2 [1]
(Cell-free assay)
PARP1 [1]
(Cell-free assay)
IC50 2.9 nM(Ki) 5.2 nM(Ki)
In vitro ABT-888 is inactive to SIRT2 (>5 μM). [1] ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. [2] ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 increases apoptosis and autophagy in H460 cells when combination with radiation. [3] ABT-888 also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 shows effective radiosensitivity in oxic H1299 cells. Furthermore, ABT-888 could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1. [4]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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JurkatM1rsT2tqdmG|ZTDBd5NigQ>?NX7KcnF[QTZiaB?=NF7yfWRFVVORM{jXU2lvcGmkaYTpc44hd2ZiUFHSVFEh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJINmdGxidnnhZoltcXS7IIfpeIghTUN3MDDv[kA{KM7:TR?=M{DqW|I{QDVyMUm5
Capan1NEfMSHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3;FbFczKGh?M{jHXWROW09?MkXsRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDCVmNCOiCpZX7lJI12fGG2ZXSgbJVu[W5iQ3HwZY4yKGOnbHzzJJdqfGhiSVO1NEBw\iB|OT63JO69VQ>?NH\NZngzPDN7OEO4Ny=>
DT40MoKxR5l1d3SxeHnjJGF{e2G7M4DJflczKGh?NI[yVGVFVVORM4jI[mN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGOqaXPr[Y4hSlKFQUKt[IVncWOrZX70JGRVPDBiY3XscJM>M3nFclI1QTJ{NUi3
ML-1NFjS[GtCeG:ydH;0bYMhSXO|YYm=M13KZ|IvPSEQvF2=NGr4TokzPCCqMnvDSG1UVw>?MUfTfY5memerc4TpZ4FtdHliZX7oZY5k\XNiVGLBTWwucW6mdXPl[EBieG:ydH;zbZMhcW5iTVytNUBk\Wyucx?=NH3jVo4zPDh7NUGzOS=>
HCT-116NFf4eopMcW6jc3WgRZN{[Xl?NWrYWpNqOC53IN88US=>NHHvU5gzPCCqNF3zRo5RSVKSIHHjeIl3cXS7IHTlZ5Jm[XOncx?=MkjVNlMxPTR{MUO=
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... Click to View More Cell Line Experimental Data

In vivo The oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. [1] ABT-888 (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, ABT-888 decreases the tumor vessel formation. [3] ABT-888 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. [4]
Features Increases the efficacy of common cancer therapies such as radiation and alkylating agents.

Protocol(Only for Reference)

Kinase Assay:

[1]

In vitro PARP assays PARP assays are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [3H]NAD+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter.

Animal Study:

[1]

Animal Models NCI-H460, H460, B16F10 and 9L xenografts in C57BL/6 mice
Formulation Formulated in solution containing 0.9% NaCl adjusted to pH 4.0
Dosages ~25 mg/kg
Administration Orally administered

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Donawho CK, et al, Clin Cancer Res, 2007, 13 (9), 2728-2737.

[2] Penning TD, et al, J Med Chem, 2009, 52(2), 514-523.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02849496 Not yet recruiting BRCA1 Gene Mutation|BRCA2 Gene Mutation|Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Stage IIIA Breast Cancer|Stage  ...more BRCA1 Gene Mutation|BRCA2 Gene Mutation|Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer|Stage IV Breast Cancer|Triple-Negative Breast Carcinoma National Cancer Institute (NCI) May 2017 Phase 2
NCT02831179 Not yet recruiting Functional Pancreatic Neuroendocrine Tumor|Malignant Somatostatinoma|Merkel Cell Carcinoma|Metastatic Adrenal Gland Pheochromocytoma|Metastatic Car  ...more Functional Pancreatic Neuroendocrine Tumor|Malignant Somatostatinoma|Merkel Cell Carcinoma|Metastatic Adrenal Gland Pheochromocytoma|Metastatic Carcinoid Tumor|Multiple Endocrine Neoplasia Type 1|Multiple Endocrine Neoplasia Type 2A|Multiple Endocrine Neoplasia Type 2B|Neuroendocrine Neoplasm|Non-Functional Pancreatic Neuroendocrine Tumor|Pancreatic Glucagonoma|Pancreatic Insulinoma|Recurrent Adrenal Cortex Carcinoma|Recurrent Adrenal Gland Pheochromocytoma|Recurrent Merkel Cell Carcinoma|Somatostatin-Producing Neuroendocrine Tumor|Stage III Adrenal Cortex Carcinoma|Stage III Thyroid Gland Medullary Carcinoma|Stage IIIA Merkel Cell Carcinoma|Stage IIIB Merkel Cell Carcinoma|Stage IV Adrenal Cortex Carcinoma|Stage IV Merkel Cell Carcinoma|Stage IVA Thyroid Gland Medullary Carcinoma|Stage IVB Thyroid Gland Medullary Carcinoma|Stage IVC Thyroid Gland Medullary Carcinoma|Thymic Carcinoid Tumor|VIP-Producing Neuroendocrine Tumor|Well Differentiated Adrenal Cortex Carcinoma|Zollinger Ellison Syndrome Vanderbilt-Ingram Cancer Center|National Cancer Institute  ...more Vanderbilt-Ingram Cancer Center|National Cancer Institute (NCI) August 2016 Phase 1
NCT02631733 Recruiting Estrogen Receptor Negative|HER2/Neu Negative|Neuroendocrine Neoplasm|Progesterone Receptor Negative|Stage IIB Cervical Cancer|Stage IIIA Cervical C  ...more Estrogen Receptor Negative|HER2/Neu Negative|Neuroendocrine Neoplasm|Progesterone Receptor Negative|Stage IIB Cervical Cancer|Stage IIIA Cervical Cancer|Stage IIIB Cervical Cancer|Stage IIIB Non-Small Cell Lung Cancer|Stage IIIC Breast Cancer|Stage IV Breast Cancer|Stage IV Cervical Cancer|Stage IV Gastric Cancer|Stage IV Non-Small Cell Lung Cancer|Stage IV Ovarian Cancer|Stage IV Small Cell Lung Carcinoma|Triple-Negative Breast Carcinoma National Cancer Institute (NCI) July 2016 Phase 1
NCT02595905 Recruiting BRCA1 Mutation Carrier|BRCA2 Mutation Carrier|Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Stage IV Breast Cancer|Tr  ...more BRCA1 Mutation Carrier|BRCA2 Mutation Carrier|Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Stage IV Breast Cancer|Triple-Negative Breast Carcinoma National Cancer Institute (NCI) July 2016 Phase 2
NCT02723864 Recruiting Neoplasms National Cancer Institute (NCI)|National Institutes of He  ...more National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) March 2016 Phase 1

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Chemical Information

Download Veliparib (ABT-888) SDF
Molecular Weight (MW) 244.29
Formula

C13H16N4O

CAS No. 912444-00-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms NSC 737664
Solubility (25°C) * In vitro DMSO 17 mg/mL (69.58 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose+0.2% Tween 80 5 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide

Tech Support

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