AN1025

AN1025 is an oral small molecule  β-catenin degrader, and is currently in the optimization phase.Wnt/β-catenin pathway is one of the key tumor-promoting signaling cascades that regulate cell cycle progression, epithelial-mesenchymal transition, angiogenesis, stemness, and tumor immune microenvironment. Aberrant activation of Wnt signaling as a result of genetic mutation has been linked to different cancers. Therefore, this pathway represents a promising target for therapeutic intervention.

 

In preclinical studies, we demonstrated that AN1025 inhibited Wnt signaling with at low concentrations. AN1025 treatment led to a reduction in β-catenin (a key component in Wnt signaling pathway) in tumor cells. In addition, human cancer cell lines with high β-catenin expression were more sensitive to AN1025, as compared to cell lines with low β-catenin expression, suggesting that β-catenin may serve as a biomarker of sensitivity to AN1025.

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AN1025 showed dose-dependent anti-tumor activities in colo205 xenograft mice models. As shown below, after a 14-day treatment, the tumor volume in mice treated with AN1025 (1.5 mg/kg, QO) was approximately 62% less than the tumor volume in the control group.

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