Valproic acid

A HDAC inhibitor that selectively inhibits the catalytic activity of class I HDACs, and induces proteasomal degradation of HDAC2; induces differentiation of carcinoma cells, transformed hematopoietic progenitor cells and leukemic blasts from AML patients; reduces tumor growth and metastasis formation in animal model.Migraine Approved (In Vitro) :Valproic acid (VPA) (0-15 mM; 24 and 72 h) inhibits Hela cell growth in a dose- and time- dependent manner.Valproic acid (10 mM; 24 h) significantly attenuates the activities of total, cytosol and nuclear HDACs.Valproic acid (0-15 mM; 24 h) induces a G1 phase arrest at 1–3 mM and a G2/M phase arrest at 10 mM, and increases the percentage of sub-G1 cells in HeLa cells. Valproic acid also induces necrosis, apoptosis and lactate dehydrogenase (LDH) release.Valproic acid (0-20 mM; 24 h) activates Tcf/Lef-dependent transcription and synergizes with lithium.Valproic acid (0-5 mM; 0-18 h) increases β-catenin levels in Neuro2A cells.Valproic acid (0-2 mM; 0-24 h) stimulates phosphorylation of AMPK and ACC in hepatocytes.Valproic acid (0-10 mM; 2 days) induces Notch1 signaling and morphologic differentiation, suppresses production of NE tumor markers in SCLC cells. (In Vivo) :Valproic acid (VPA) (500 mg/kg; i.p.; daily for 12 days) inhibits tumor angiogenesis in mice transplanted with Kasumi-1 cells.Valproic acid (350 mg/kg; i.p.; once) enhances social behavior in rats.Valproic acid (0.26% (w/v) ; p.o. via drinking water; 14 days) decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice without hepatotoxicity.