Development Of Ur214-9, A Novel Septin Inhibitor, For The Treatment Of Endometrial Cancer

Objective: Septins are cytoskeletal proteins involved in cell migration, proliferation, and cytokinesis. Methylation of septin-9 is a clinical biomarker in colorectal cancer, and deranged expression of other septins has been described in other malignancies, including gynecologic cancers. We sought to characterize the expression profile of septin paralogs in endometrial cancer and establish their association with mortality. There are currently no clinically available therapies targeting septin protein activity. We have developed a first-in-class small molecule septin inhibitor, UR214-9, and evaluated this compound’s cytotoxic effect against endometrial cancer in vitro. Endometrial cancer also displays aberrant pathway regulation on HER2, FGFR2, PI3K/AKT and/or β-catenin signaling. The effect of UR214-9 on these pathways was also investigated.