For research use only. Not for therapeutic Use.
NVP-TNKS656（Cat No.:I001613）is a selective inhibitor of tankyrase, a poly(ADP-ribose) polymerase (PARP) enzyme involved in the regulation of Wnt/β-catenin signaling and telomere maintenance. By inhibiting tankyrase, NVP-TNKS656 disrupts the stabilization of β-catenin, leading to the suppression of Wnt signaling, which is crucial in cancer cell proliferation, especially in tumors with aberrant Wnt activation. It also affects telomere elongation by inhibiting telomere-associated protein interactions. NVP-TNKS656 is primarily used in cancer research for targeting Wnt-driven cancers, providing insights into potential therapeutic strategies for tumors reliant on this pathway.
| Catalog Number | I001613 |
| CAS Number | 1419949-20-4 |
| Synonyms | N-(cyclopropylmethyl)-N-((4-hydroxy-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)methyl)-2-(4-(4-methoxybenzoyl)piperidin-1-yl)acetamide |
| Molecular Formula | C27H34N4O5 |
| Purity | ≥95% |
| Target | tankyrase |
| Solubility | DMSO: ≥ 40 mg/mL |
| Storage | Store at -20°C |
| IC50 | 6 nM [1] |
| IUPAC Name | N-(cyclopropylmethyl)-2-[4-(4-methoxybenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide |
| InChI | InChI=1S/C27H34N4O5/c1-35-21-6-4-19(5-7-21)26(33)20-8-11-30(12-9-20)16-25(32)31(14-18-2-3-18)15-24-28-23-10-13-36-17-22(23)27(34)29-24/h4-7,18,20H,2-3,8-17H2,1H3,(H,28,29,34) |
| InChIKey | DYGBNAYFDZEYBA-UHFFFAOYSA-N |
| SMILES | COC1=CC=C(C=C1)C(=O)C2CCN(CC2)CC(=O)N(CC3CC3)CC4=NC5=C(COCC5)C(=O)N4 |
| Reference | 1:J Med Chem. 2013 Aug 22;56(16):6495-511. doi: 10.1021/jm400807n. Epub 2013 Aug 13. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor.Shultz MD,Cheung AK,Kirby CA,Firestone B,Fan J,Chen CH,Chen Z,Chin DN,Dipietro L,Fazal A,Feng Y,Fortin PD,Gould T,Lagu B,Lei H,Lenoir F,Majumdar D,Ochala E,Palermo MG,Pham L,Pu M,Smith T,Stams T,Tomlinson RC,Touré BB,Visser M,Wang RM,Waters NJ,Shao W, PMID: 23844574 DOI: 10.1021/jm400807n </br><span>Abstract:</span> Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies. |
