JW74

• CAT Number: I005177
• CAS Number: 863405-60-1
• Molecular Formula: C24H20N6O2S
• Molecular Weight: 456.5
• Purity: ≥95%
• Target: tankyrase
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 790 nM
• InChIKey: KRIKILRRJCIWNB-UHFFFAOYSA-N

JW74 is an efficient and specific inhibitor of the canonical Wnt signaling. JW74 shows a reduction of canonical Wnt signaling in the ST-Luc assay with IC50 values of 790 nM.IC50 value: 790 nMTarget: WntJW74 increases concentration of AXIN2 and decrease the active form of β-catenin in SW480 colorectal cancer cells. [2] The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines.[1]

Reference

1:Cancer Med. 2014 Feb;3(1):36-46. doi: 10.1002/cam4.170. Epub 2013 Dec 17. The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines.Stratford EW,Daffinrud J,Munthe E,Castro R,Waaler J,Krauss S,Myklebost O, PMID: 24403055 PMCID: PMC3930388 DOI: 10.1002/cam4.170 Abstract: Wnt/β-catenin is a major regulator of stem cell self-renewal and differentiation and this signaling pathway is aberrantly activated in a several cancers, including osteosarcoma (OS). Attenuation of Wnt/β-catenin activity by tankyrase inhibitors is an appealing strategy in treatment of OS. The efficacy of the tankyrase inhibitor JW74 was evaluated in three OS cell lines (KPD, U2OS, and SaOS-2) both at the molecular and functional level. At the molecular level, JW74 induces stabilization of AXIN2, a key component of the β-catenin destruction complex, resulting in reduced levels of nuclear β-catenin. At the functional level, JW74 induces reduced cell growth in all three tested cell lines, in part due to a delay in cell cycle progression and in part due to an induction of caspase-3-mediated apoptosis. Furthermore, JW74 induces differentiation in U2OS cells, which under standard conditions are resistant to osteogenic differentiation. JW74 also enhances differentiation of OS cell lines, which do not harbor a differentiation block. Interestingly, microRNAs (miRNAs) of the let-7 family, which are known tumor suppressors and inducers of differentiation, are significantly upregulated following treatment with JW74. We demonstrate for the first time that tankyrase inhibition triggers reduced cell growth and differentiation of OS cells. This may in part be due to an induction of let-7 miRNA. The presented data open for novel therapeutic strategies in the treatment of malignant OS.© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.