Published TCIMAIL newest issue No.197
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Tankyrase Inhibitor
No.174(July 2017)
XAV 939 (1), which was discovered by a chemical genetic screening, is a small molecule inhibitor of tankyrase.1) 1 inhibits tankyrase 1 and 2 with IC50 values of 11 and 4 nM, respectively (Table). Inhibition of tankyrase by 1 stabilizes axin, resulting in stimulating β-catenin degradation. The destabilization of β-catenin inhibits Wnt signal pathway. Therefore, 1 is used as an antagonist of Wnt signaling.
β-Catenin plays important roles in pluripotency of stem cells.2) Davidson et al. reported that loss of hESCs self-renewal is promoted by activation of Wnt/β-catenin signaling and 1 blocks the loss.3) In addition, conversion of mouse EpiSCs to naïve-like PSCs (rESCs) is enhanced by inhibition of nuclear translocation of β-catenin with 1.4) 1 also induces cardiomyocyte differentiation from mouse and human ESCs.5,6)
EpiSCs: epiblast stem cells
PSCs: pluripotent stem cells
rESCs: reverted embryonic stem cells
PSCs: pluripotent stem cells
rESCs: reverted embryonic stem cells
Table. Inhibitoryactivity of XAV 9391)
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References
- 1)Tankyrase inhibition stabilizes axin and antagonizes Wnt signaling
- 2)β-Catenin in pluripotency: Adhering to self-renewal or wnting to differentiate?
- 3)β-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4
- 4)Successful reprogramming of epiblast stem cells by blocking nuclear localization of β-catenin
- 5)Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/β-catenin signaling
- 6)Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm
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