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Stanton McHardy

UTSA chemists including Stanton McHardy, a professor in the UTSA Department of Chemistry, are working to produce molecules that mimic estrogen activity at ER-beta without the known side effects associated with increased estrogen, such as breast tenderness and vaginal bleeding in women and fatigue and sweating in men.

“My lab will design, synthesize and optimize small-molecule inhibitors of ER-beta,” McHardy said. “Our ultimate goal is to identify a structurally novel ER-beta agonist, a molecule that acts like estrogen, that can be developed clinically.”

McHardy’s involvement in the project is personal. His older sister died of an inoperable GBM tumor for which there were no effective treatments. He says the project has been an extremely efficient and productive collaboration between his laboratory and his research partners.

McHardy is director of the Center for Innovative Drug Discovery (CIDD), a joint initiative of UTSA and UT Health San Antonio that is supported by funding from the Cancer Prevention and Research Institute of Texas (CPRIT). Grants provided by CPRIT were instrumental in offering support for preliminary data generation, which bolstered the team’s NCI-funded proposal.

CIDD is comprised of four collaborating core research facilities: a High-Throughput In Vitro Screening (HTSF) Facility and Computer-Aided Drug Design (CADD) Facility located at UT Health San Antonio and a Medicinal Chemistry Core Facility (MCCF) and a Pre-Clinical Pharmacology Core Facility (PCPC) at UTSA. The center’s mission is to provide a diverse array of core facilities and expertise to facilitate the translation of basic scientific discoveries into tangible pre-clinical candidate drugs that can be later developed into clinical therapies.

Karinel Nieves-Merced and Michael Tidwell, special research associates at CIDD and staff chemists at UTSA, have contributed to the research program. Nieves-Merced assisted in the early compound design stages of the program, and Tidwell synthesized the compounds and characterized their structure.

“This research proposal is based on strong preliminary data showing that ER-beta exerts tumor-suppressive functions in glioblastoma,” said Ratna K. Vadlamudi, professor in the Department of Obstetrics and Gynecology at UT Health San Antonio. “This proposal will develop novel ER-beta drugs that promote tumor suppression, leading to a new therapeutic modality to treat GBM.”

The scientists will go through iterations of ER-beta agonists to develop a novel clinical strategy and bring hope to patients and families affected by GBM. The goal is to move forward with completion of validation using preclinical models and then to test the molecules in clinical trials in two to three years.

“This is a great example of the drug discovery happening here at UTSA that will have real impact on cancer treatment,” said Audrey Lamb, professor and chair of the UTSA Department of Chemistry. “I am very excited by the work Dr. McHardy and his team are doing, which has clear potential for providing a therapeutic strategy in the near future.”