NVP-TNKS656

• CAT Number: I001613
• CAS Number: 1419949-20-4
• Molecular Formula: C27H34N4O5
• Molecular Weight: 494.6
• Purity: ≥95%
• 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
• 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

NVP-TNKS656 (Cat No.:I001613) is a highly potent and selective inhibitor of TNKS2 (Tankyrase 2), an enzyme involved in cellular processes such as Wnt/β-catenin signaling and telomere maintenance. It exhibits an IC50 of 6 nM against TNKS2 and demonstrates more than 300-fold selectivity over PARP1 and PARP2, two related enzymes. NVP-TNKS656 is orally active and holds potential for therapeutic applications in diseases related to dysregulated Wnt signaling, such as cancer and fibrosis.

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 Abstract: 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.