Investigation of Small Molecule Inhibitors Targeting βCatenin/TCF4 Interaction in Ovarian Cancer Cell Lines

Abstract

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. The development of chemoresistance and relapse is a major challenge in treating ovarian cancer. The Wnt/β-catenin pathway plays critical roles in embryonic development and adult homeostasis. The aberrant activation of β-catenin and its interaction with its co-activator TCF4 is implicated in the progression of EOC; therefore, targeting and inhibiting this interaction is desirable for the development of targeted therapies. Previous studies have identified a small molecule inhibitor of β-catenin known as C10, and novel analogues of C10, C45-C62 have been synthesized in-house. In this study, C45-C62 have been characterized through structure-activity relationship analyses and functional assays to determine their direct binding to β-catenin and antitumour effects. Optimization of C10 and its analogues could lead to potential development of a novel β-catenin/TCF4 inhibitor for ovarian cancer treatment.