In this study, we synthesized and characterized a new chemical library of highly functionalized 5-hydroxy-2H-pyrrol-2-ones by using an in-silico modeling approach [30,31] followed by phenotype- and ERα-based screening assays in ERα-positive breast and endometrial cancer cells in order to identify new therapeutic strategies that overcome major limitations of current ER+ BC treatments. The gene discussed is ESR1; the disease is endometrial cancer.