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JW74

CAS No. : 863405-60-1

MCE 国际站：JW74

产品活性：JW74 拮抗 LiCl 诱导的经典 Wnt 信号传导的激活，IC₅₀ 为 420 nM。

研究领域：Stem Cell/Wnt

作用靶点：Wnt

In Vitro: JW74 shows a reduction of canonical Wnt signaling in the ST-Luc assay with an IC₅₀ of 790 nM. The effect of tankyrase inhibition on cellular viability is tested by performing an MTS assay. The cellular viability of U2OS cells treated for 72 h treatment with 10 μM JW74 is reduced to 80%, relative to DMSO-treated cells. Flow cytometry is also performed to determine the expression marker Ki-67 in U2OS following 48 h treatment with DMSO or 10 uM JW74. Ki-67 expression is reduced from 97.5% in DMSO-treated cells to 86.7% in JW74-treated cells.

In Vivo: The in vivo efficacy of JW74 is tested using SW480 cell xenografts. A relatively high dose of JW74 (150 or 300 mg/kg) is used because of a rapid compound degradation in the organism as indicated in the human liver microsome analysis (t_1/2=2.5 minutes) and in pharmacokinetic analyses (after per oral injections: t_1/2=30 minutes and intravenous injections: t_1/2=15 minutes). The presence of JW74 in tumors and plasma is identified by mass spectrometry. JW74 concentration in tumors is in the range 4.2 to 72.1 μmol/kg for JW74 150 mg/kg, 1.9 to 11.1 μmol/kg for JW74 300 mg/kg, and 2.8 μM in plasma for both doses.

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