This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) to the Regents of the University of Minnesota for $549,474 is focused on identifying and validating specific inhibitors of the phosphoribosylformylglycinamidine synthase (PFAS) enzyme as a new class of purine antimetabolites for cancer treatment.
The key objectives are to: 1) identify small molecule inhibitors of PFAS enzyme activity, and 2) validate the activity, selectivity, mechanism of action, and preliminary structure-activity relationship of the hit compounds. This work leverages the university's development of a novel fluorescent assay for PFAS activity and cryo-EM structural analysis of the human PFAS protein. The goal is to produce validated PFAS inhibitors that can be used to elucidate the role of PFAS and nucleotide metabolism in liver cancer progression, with the potential to transform liver cancer treatment and improve patient outcomes. The award period runs from March 1, 2025 to February 29, 2028.
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