5.00556

Tankyrase1/2 Inhibitor V, WIKI4

• Synonym(s): Tankyrase1/2 Inhibitor V, WIKI4, 2-(3-((4-(4-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)sulfanyl)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, Wnt Pathway Inhibitor XVIII, TNKS1/2 Inhibitor V
• Empirical Formula (Hill Notation): C₂₉H₂₃N₅O₃S
• CAS Number: 838818-26-1
• Molecular Weight: 521.59
• MDL number: MFCD05885187
• UNSPSC Code: 12352200
• PubChem Substance ID: 2984337
• NACRES: NA.77

Properties

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: powder
• potency: 15 nM IC₅₀
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: pale yellow
• solubility: DMSO: 5 mg/mL
• storage temp.: 2-8°C
• SMILES string: COC1=CC=C(C=C1)N2C(=NN=C2SCCCN3C(=O)C4=CC=CC5=C4C(=CC=C5)C3=O)C6=CC=NC=C6
• InChI: 1S/C29H23N5O3S/c1-37-22-11-9-21(10-12-22)34-26(20-13-15-30-16-14-20)31-32-29(34)38-18-4-17-33-27(35)23-7-2-5-19-6-3-8-24(25(19)23)28(33)36/h2-3,5-16H,4,17-18H2,1H3
• InChI key: RNUXIZKXJOGYQP-UHFFFAOYSA-N

Description

General description

A cell-permeable triazole derivative that acts as a reversible TNKS inhibitor (IC₅₀ = 15 nM in cell-free TNKS2 auto-ribosylation assays) and selectively inhibits Wnt/β-catenin, but not NF-κB, TGFβ, or retinoic acid, signaling pathway-dependent reporter activity. Although structurally distinct from XAV939, both compounds are shown to induce basal axin1/2 protein accumulation in DLD1 colon cancer cells with mutant APC (2.5 µM; 2 to 4 h) and prevent Wnt3a-induced axin1 protein degradation and β-catenin accumulation in A375 melanoma cells (1 µM; and up to 24 h) with similar potency. Likewise, WIKI4 also effectively inhibits the Wnt/β-catenin pathway-dependent growth of DLD1 (37% and 67% inhibition of colony formation in 10 days, respectively, in the presence of 0.1 and 1 µM WIKI4).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
TNKS2

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Followig reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

James, R.G., et al. 2012. PLoS. One.7, e50457.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable