GAPDH Inhibitors

Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) is traditionally known as a key enzyme in glycolysis, catalyzing the sixth step of the pathway where glyceraldehyde-3-phosphate is converted into 1,3-bisphosphoglycerate. Beyond its metabolic role, GAPDH participates in various non-glycolytic processes, including nuclear RNA export, DNA repair, and cell death. Its function is regulated through various post-translational modifications, allowing it to interact with different cellular components and partake in cellular signaling pathways. GAPDH's involvement in apoptosis and oxidative stress responses links it to neurodegenerative diseases and cancer. It's also implicated in the regulation of autophagy and inflammation, indicating a broader role in cellular homeostasis and stress response. Due to these diverse functions, GAPDH signaling plays a significant role in the overall cellular function and health. Targeting GAPDH with small molecules for disruption or inhibition offers potential strategies for characterization of TCA related pathways, particularly in diseases where GAPDH plays a pathological role. Small molecule inhibitors could be designed to bind directly to the active site of GAPDH, inhibiting its glycolytic activity and thereby impacting cancer cells that rely heavily on glycolysis. Other strategies might involve blocking GAPDH's interactions with other proteins or nucleic acids, thus influencing its non-glycolytic functions like apoptosis or autophagy. Modulators of post-translational modifications of GAPDH could also be a focus, altering its activity and interaction with other cellular pathways.