BPTES

BPTES is a small-molecule inhibitor of the mitochondrial enzyme glutaminase GLS1. Glutaminase converts glutamine to glutamate, feeding the production of α-ketoglutarate for the tricarboxylic acid cycle and biosynthesis. BPTES acts as an allosteric inhibitor that binds to GLS1 and reduces its catalytic activity, thereby limiting glutaminolysis in cells.

In cell and enzyme assays, BPTES demonstrates selectivity for GLS1 over GLS2 and other related enzymes, with activity in the low micromolar range in vitro. In cellular systems, effective concentrations vary by cell type and glutamine dependence; some GLS1-dependent cancer cell lines show reduced proliferation and metabolic flux when treated with BPTES.

Usage and context: BPTES is widely used as a research tool to explore the role of glutamine metabolism in cancer, neuroscience, and immunology. It is not approved for clinical use. Because of limited solubility in water, it is typically dissolved in organic solvents like DMSO for in vitro experiments and may require formulation for in vivo work.

Discovery and related compounds: BPTES was described as a potent GLS1 allosteric inhibitor identified through screening and structure-based design. It has served as a lead compound for the development of more potent GLS1 inhibitors, such as CB-839 (telaglenastat), which has entered clinical development. Researchers continue to study BPTES alongside newer inhibitors to understand GLS1 dependency in tumors and other tissues.