Selective in vitro and in vivo anti-tumor activity of PRLX 93936 in biological models of melanoma and ovarian cancer

14586 Background: PRLX 93936 is a novel small molecule exhibiting therapeutic potential in an array of in vitro and in vivo tumor models many with limited treatment options such as melanoma. Developed and characterized in cell-based phenotypic assays, PRLX 93936 is a product of extensive SAR work originating from a small molecule identified in a synthetic lethal screen against isogenic cell lines engineered to differentially express several genes including activated RasV12. Methods: Assays measuring cell survival, cytostasis, cell cycle activity and mechanisms of death were employed to characterize the biological activity of the compound. Structural analogs were designed and tested for antiproliferative activity against normal cells and lines derived from tumors with dissimilar causative mutations. Western blotting and mRNA analyses were used to characterize the Ras pathway activation status of the cell panel. In vivo testing of the compound was performed in mice harboring xenografts of human tumor origin...