Clinical stage drugs utilizing cellular metabolism pathways

We have gathered sufficient evidence to claim that inhibition of glycolysis impairs proinflammatory responses while favoring antiinflammatory outcomes. Specifically, modulation of glycolytic reprogramming can predominantly affect inflammatory immune or cancer cells, offering low on-target toxicity. Not surprisingly, this has been exploited by researchers focused on the development of novel therapeutic interventions. Here, we describe emerging metabolic targets and profile clinically approved and clinical-stage drugs that target metabolism as a critical mechanism of action. Therapies targeting glycolysis include both pharmacologic inhibitors of key enzymes and receptors antagonists, while approaches focused on the citric acid—or tricarboxylic acid cycle (TCA)—cycle additionally explore analogs of metabolites that possess cytokine-like properties. There are numerous preclinical programs and patents generated at university start-ups in addition to many biotech and big pharma-led projects aimed at targeting glycolysis and citric acid pathways clinically. Contrary to expectations, programs based on modulation of glycolysis and the citric acid cycle seem to hold the most promise in cancers, genetic, and autoimmune diseases, rather than the classical definition of physiological metabolic diseases.