UTSA chemists including Stanton McHardya professor in the UTSA Department of Chemistry, are working to produce molecules that mimic estrogen activity in 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,” said McHardy. “Our ultimate goal is to identify a new structural ER-beta agonist, an estrogen-like molecule, 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 lab and his research partners.
McHardy is the director of 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 providing support for preliminary data generation, which strengthened the NCI-funded team’s proposal.
CIDD consists of four core collaborative research facilities: a high-throughput in vitro screening facility (HTSF) and a computer-aided drug design (CADD) facility located at UT Health San Antonio and a Medicinal Chemistry Core Facility (MCCF) and a Clinical Pharmacology Core Facility (PCPC) at UTSA. The center’s mission is to provide a range of essential facilities and expertise to facilitate the translation of basic scientific discoveries into tangible preclinical drug candidates that can later be 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 stages of the program’s complex design, and Tidwell synthesized the compounds and characterized their structure.
“This research proposal is based on strong preliminary data showing that ER-beta exerts tumor suppressor functions in glioblastoma,” said. Ratna K. Vadlamudi, professor in the Department of Obstetrics and Gynecology at UT Health San Antonio. “This proposal will develop new ER-beta drugs that promote tumor suppression, leading to a new therapeutic modality for the treatment of GBM.”
Scientists will go through iterations of ER-beta agonists to develop a new clinical strategy and bring hope to patients and families affected by GBM. The goal is to move forward with completing validation using preclinical models and then test the molecules in clinical trials in two to three years.
“This is a great example of drug discovery happening here at UTSA that will have a real impact on cancer treatment,” said Audrey Lamb, professor and chair of the UTSA Department of Chemistry. “I am very excited by the work that Dr. McHardy and his team are doing, which has clear potential to provide a therapeutic strategy in the near future.”