siRNA (PHGDH)

siRNA (PHGDH) is a small interfering RNA designed to silence the expression of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine biosynthetic pathway. In preclinical research, particularly in models of heart failure with preserved ejection fraction (HFpEF), this siRNA is used to investigate the role of serine metabolism in myocardial energy and redox balance. Research presented at the ACC 2025 meeting indicates that PHGDH inhibition leads to significant reductions in ATP, GTP, and mitochondrial DNA, as well as impaired mitochondrial oxygen consumption and increased oxidative stress in the failing heart. While primarily utilized as a research tool to elucidate metabolic inflexibility in heart failure, it highlights the serine metabolic pathway as a potential therapeutic target for metabolic intervention.

Other names

PHGDH siRNAsiRNA targeting PHGDH