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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.
