5-oxo-2-tetrahydrofurancarboxylic acid

5-oxo-2-tetrahydrofurancarboxylic acid (also known as 5-oxo or S-5-oxo) is a small molecule, second-generation competitive and reversible inhibitor of mitochondrial proline dehydrogenase (PRODH). PRODH is an inner mitochondrial membrane flavoprotein that catalyzes the first step of proline catabolism, converting L-proline to delta-1-pyrroline-5-carboxylate, which is functionally linked to electron transport and ATP production under nutrient stress. Developed preclinically by the Buck Institute for Research on Aging, 5-oxo-2-tetrahydrofurancarboxylic acid is being investigated as a potential cancer therapeutic, particularly for breast cancer subtypes. By inhibiting PRODH, the compound induces mitochondrial stress and impairs cancer cell growth. Preclinical studies suggest that its anticancer efficacy is significantly enhanced when combined with glutaminase (GLS1) inhibitors (such as telaglenastat) or p53 upregulators (such as MDM2 antagonists), exploiting synthetic lethal metabolic interactions under hypoxic conditions.

Other names

(2R)-5-oxotetrahydro-2-furancarboxylic acid(2S)-5-oxotetrahydro-2-furancarboxylic acid(R)-(-)-5-oxo-2-tetrahydrofurancarboxylic acid(R)-5-oxotetrahydrofuran-2-carboxylic acid(S)-(+)-5-oxo-2-tetrahydrofurancarboxylic acid(S)-5-oxotetrahydrofuran-2-carboxylic acid5-oxo5-oxotetrahydrofuran-2-carboxylic acidS-5-oxoS5-oxoS 5-oxoS-5-oxo-2-tetrahydrofurancarboxylic acidS5-oxo-2-tetrahydrofurancarboxylic acidS 5-oxo-2-tetrahydrofurancarboxylic acidS-Hothf