journal contribution
posted on 2023-03-31, 23:21 authored by Liang You, Zhidong Xu, Chandanamali Punchihewa, David M. Jablons, Naoaki Fujii Supplementary Material from Evaluation of a chemical library of small-molecule Dishevelled antagonists that suppress tumor growth by down-regulating T-cell factor–mediated transcription
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ARTICLE ABSTRACT
We describe the rational generation of small-molecule agents that suppress tumor cell growth by down-regulating canonical Wnt signaling. We first produced a chemical library of the derivatives of indole-2-ketones and carbinols; we then screened them by using scalable assays of biochemical antagonism of Dishevelled-1 PDZ domain interactions and cell-based assays of Dishevelled-1–driven T-cell factor–mediated transcription. Compounds showing parallel effects in these assays were tested for selective induction of apoptosis in cancer cells. A new compound (24) that met the criteria for high biochemical antagonism, T-cell factor–mediated transcription, and induction of tumor-selective apoptosis was found to significantly suppress the growth of tumor xenografts in mice. [Mol Cancer Ther 2008;7(6):1633–8]
