XAV-939的生物活性

XAV939 is a small molecule and selective Wnt pathway β-catenin-mediated transcription inhibitor and axin stabilizing agent with IC50 of 11 and 4 nM for the inhibition of TNKS1 and TNKS2, respectively.
IC50 Value: 11 nM(TNKS1);  4 nM(TNKS2)
Target: TMKS1/2; β-catenin
in vitro: XAV-939 specifically inhibits tankyrase PARP activity. XAV-939 dramatically decreases DNA-PKcs protein levels, confirming the critical role of tankyrase poly-ADP-ribosylation activity in maintaining stability of the DNA-PKcs protein. The greatest reduction of DNA-PKcs protein levels (< 25% relative expression compared to DMSO treated controls) occurs at 12 hours with 1.0 μM XAV-939 exposure. Treatment of human lymphoblasts with 1.0 μM XAV-939 results in marked elevation of tankyrase 1 levels. XAV-939 is axin stabilizing agent. XAV-939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. XAV-939 stabilizes axin by blocking the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. XAV-939 deregulates the Wnt/b-catenin pathway which has been implicated in many cancers.
in vivo: N/A
 

相關(guān)文獻(xiàn)

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