NIH Reporter #1R16GM159657-01A1

Design, synthesis and biological evaluation of potent and selective pyruvate carboxylase (PC) inhibitors for studying cancer cell metabolism

NIH awarded a research grant to New York Institute of Technology to develop potent and selective inhibitors of pyruvate carboxylase for cancer metabolism studies, using structure-based drug discovery and interdisciplinary approaches.

Description

This project aims to develop small molecule inhibitors that are potent and selective to pyruvate carboxylase (PC) to study cancer cell metabolism, potentially leading to new chemotherapeutic agents. The project employs a structure-based drug discovery approach focusing on developing an extended structure-activity relationship on an existing scaffold and chemically exploiting two weak allosteric PC inhibitors to generate molecules with increased potency and selectivity. The compounds will be characterized through multiple in-vitro screening assays, kinetic, cellular, and structural studies. The project involves an interdisciplinary team including undergraduate students, offering exposure to medicinal chemistry, protein biochemistry, cell biology, and structural biology.

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