Home DNA Damage/DNA Repair PARP inhibitor NVP-TNKS656 For research use only.

NVP-TNKS656

NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2.

NVP-TNKS656 Chemical Structure

NVP-TNKS656 Chemical Structure

CAS No. 1419949-20-4

Purity & Quality Control

NVP-TNKS656 Related Products

Signaling Pathway

PARP Signaling Pathways

PARP Signaling Pathway

Biological Activity

Description NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2.
Targets
TNKS2 [1]
(Cell-free assay)
6 nM
In vitro
In vitro

In vitro, NVP-TNKS656 shows low to moderate microsomal ER values across species and high solubility. [1]

In PI3K or AKT inhibitor-resistant cells, NVP-TNKS656 blocks Wnt/β-Catenin pathway and promotes apoptosis. [2]
Kinase Assay Tankyrase AutoPARsylation Assay
PARP catalytic activity is monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of nicotinamide. The autoPARsylation reactions are performed at room temperature in 384-well Greiner flat-bottom plates. The final reaction mixture contains 2.5% DMSO and inhibitors with concentrations ranging from 0.0001 to 18.75 μM. GST-TNKS2P, GST-TNKS1P, PARP1, and PARP2 enzymes are used at final concentrations or 5, 5, 5, and 2 nM, respectively. The nicotinamide concentration in the resulting supernatants is measured by LC-MS. The % inhibition is calculated as follows: (control – sample)/(control – background) × 100. “Control” is the average value of eight wells without compound, and “background” is the average of eight wells mixed with 5× quenching solution measured prior to initiation of the reaction.
In Vivo
In vivo

In mice, NVP-TNKS656 displays low clearance and volume of distribution, and exhibits good exposure and moderate oral bioavailability. In MMTV-Wnt1 tumor bearing athymic nude mice, NVP-TNKS656 (350 mg/kg, p.o.) stabilizes Axin1 protein and reduces the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. [1]

In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth. [2]
Animal Research Animal Models Athymic female nude mice bearing MMTV-Wnt1 tumors
Dosages 350 mg/kg
Administration p.o.

Chemical Information & Solubility

Molecular Weight 494.58 Formula

C27H34N4O5
CAS No. 1419949-20-4 SDF Download NVP-TNKS656 SDF
Smiles COC1=CC=C(C=C1)C(=O)C2CCN(CC2)CC(=O)N(CC3CC3)CC4=NC5=C(COCC5)C(=O)N4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (202.19 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 10 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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