NVP-TNKS656

Catalog No.S7238 Batch:S723802

Technical Data

Formula	C₂₇H₃₄N₄O₅
Molecular Weight	494.58	CAS No.	1419949-20-4
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (202.19 mM)
		Ethanol	10 mg/mL (20.21 mM)
		Water	Insoluble
* <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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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, 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]

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]

Protocol (from reference)

Kinase Assay:^{^[1]}	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.
Animal Study:^{^[1]}	Animal Models Athymic female nude mice bearing MMTV-Wnt1 tumors Dosages 350 mg/kg Administration p.o.

Kinase Assay:^{^[1]}

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.

Animal Study:^{^[1]}

Animal Models
Athymic female nude mice bearing MMTV-Wnt1 tumors
Dosages
350 mg/kg
Administration
p.o.

References

Selleck's NVP-TNKS656 has been cited by 5 publications

TNF-NF-κB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons [ Cell, 2024, 187(14):3671-3689.e23]	PubMed: 38866017
Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression [ bioRxiv, 2023, 2023.07.19.549714]	PubMed: 37577543
Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression [ bioRxiv, 2023, 2023.07.19.549714]	PubMed: 37577543
Identification of novel target for osteosarcoma by network analysis [ Med Sci Monit, 2018, 24: 5914–5924]	PubMed: 30144309
Identification of Novel Target for Osteosarcoma by Network Analysis [Zhi LQ, et al. Med Sci Monit, 2018, 24:5914-5924]	PubMed: 30144309

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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