Triple negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor a (ERα), progesterone receptor (PR), and HER2. While TNBC constitutes about 15% of all breast cancers, mortality of patients with TNBC is disproportionately higher than those with other subtypes of breast cancer.  ERβ is expressed in more than half of breast cancer cases across all major subtypes, thus providing the opportunity of stimulating its antitumor activity as a potential therapeutic approach.  Previous work in Dr. Rong Li’s lab (UTHSCSA) uncovered eye absent 2 (EYA2) as the tyrosine phosphatase that directly dephosphorylates pY36-ERb in vitro and in vivo.  EYA2 is a known oncoprotein in ovarian and breast cancers. This work focused on testing the central hypothesis that pharmacological targeting of the oncoprotein EYA2 with small molecule inhibitors can effectively inhibit breast and ovarian cancer cell proliferation.  Due to the EYA2 x-ray structural and modeling data available, along with some known small molecule inhibitors of EYA2, the program was perfectly positioned for designing, synthesizing and testing novel EYA2 inhibitors.  This poster will highlight our collaborative program results, which has produced several new lead EYA2 inhibitors producing good inhibition (IC50 1-5 uM) in the MTT assay using triple negative breast cancer cells MDA-MB-468.  New compound design, synthesis, structure-activity relationships and in vitro data on lead analogs will be presented.<br/>

Discovery of novel small molecule inhibitors of oncoprotein EYA2 for breast and ovarian cancers

253rd National Meeting (2017)

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