In conclusion, we have sought to make more potent RPN13 inhibitors utilizing a rational development approach to judiciously modify substituents around the core unit of RA190 and, after several rounds of this, RA375 emerged as a promising compound based on pharmacodynamics and its reduction of tumor burden and prolongation of the survival of mice carrying an orthotopic human ovarian cancer xenograft. This evidence concerns the gene ADRM1 and ovarian cancer.