Valproic acid (Sodium Valproate) sodium is an orally active 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 activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium is used in the treatment of epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches[2].IC50 & Target: IC50: 400 μM (HDAC1), 0.5-2 mM (HDAC)HDAC2In 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[2].
Valproic acid (0-5 mM; 0-18 h) increases β-catenin levels in Neuro2A cells[2].
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.