Home DNA Damage/DNA Repair PARP inhibitor NVP-TNKS656

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NVP-TNKS656 PARP inhibitor

Cat.No.S7238

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 PARP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 494.58

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Quality Control

Batch: Purity: 99.85%
99.85

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (202.19 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 10 mg/mL

Water : Insoluble

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In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight 494.58 Formula

C27H34N4O5

 Storage (From the date of receipt)
CAS No. 1419949-20-4 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles COC1=CC=C(C=C1)C(=O)C2CCN(CC2)CC(=O)N(CC3CC3)CC4=NC5=C(COCC5)C(=O)N4

Mechanism of Action

Targets/IC50/Ki
TNKS2
(Cell-free assay)
6 nM
In vitro

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

In PI3K or AKT inhibitor-resistant cells, this compound blocks Wnt/β-Catenin pathway and promotes apoptosis.

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 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, this compound (350 mg/kg, p.o.) stabilizes Axin1 protein and reduces the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%.

In colorectal cancer PDX models, this chemical reduces nuclear β-catenin, reverts such resistance, and represses tumor growth.

References

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