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PGC-1α activators and inhibitors act on the coactivator that controls mitochondrial biogenesis. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) binds nuclear receptors and other transcription factors to raise their activity. PGC-1α was identified in 1998 as a cold-inducible coactivator in brown fat and skeletal muscle. A 1999 study showed that it drives mitochondrial biogenesis and respiration through nuclear respiratory factors. ZLN005 was reported in 2013 to increase PGC-1α transcription in muscle cells. SR 18292, described in 2017, suppresses PGC-1α gluconeogenic activity by increasing its acetylation. MitoPBN and mogroside VI B are listed as PGC-1α modulators, and the histone deacetylase inhibitor valproic acid is also filed here.
Synonyms: Depakin; Erganyl; Stavzor; Valproate
Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.
Synonyms: Sodium Valproate
Valproic acid sodium salt (Sodium Valproate) is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2.
SR 18292 is a PGC-1α inhibitor. It reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of T2D.
Ac-SVVVRT-NH2 is a PGC-1α modulator that modulates the activity of the human PGC-1α promoter (114%). Ac-SVVVRT-NH2 increases PGC-1α mRNA (125%) and accumulation of intracellular lipids (128%) in subcutaneous human adipocytes. Ac-SVVVRT-NH2 can be used in the research of diseases which is modulated by PGC-1α.
MitoPBN is an AMPK/SIRT3/PGC-1α modulator that enhances mitochondrial function by acting as a reactive oxygen species scavenger. This compound promotes mitochondrial biogenesis through increased AMPK phosphorylation, restoration of SIRT3 expression, and upregulation of PGC-1α. MitoPBN is effective in regulating glucose metabolism, as it decreases blood glucose levels by inhibiting hepatic gluconeogenesis and enhancing glucose uptake, while also improving ATP production and maintaining mitochondrial membrane potential. Additionally, it can reduce apoptosis and enhance sperm motility and membrane integrity, making it a valuable reagent for research related to diabetes and metabolic disorders.
