N-Propargylglycine is a brain-penetrant, orally active PRODH inhibitor. It works by covalently modifying enzyme-bound FAD and active site lysine, leading to enzyme structural distortion, protein decay, and irreversible inhibition of proline and 4-hydroxyproline catabolism. It can induce UPRmt, upregulate mitochondrial chaperones, and enhance mitochondrial proteostasis.
- Brain-penetrant and orally active.
- Irreversibly inhibits proline oxidation.
- Induces mitochondrial unfolded protein response.
- Blocks astrocytic L-proline consumption.
- Stimulates neural processes and increases brain amino acid levels.
- Reduces hyperoxaluria and prevents calcium oxalate stone formation.
- Used in research for breast cancer, neurodegenerative disorders, and primary hyperoxaluria.