Valproic acid (VPA) sodium (2:1) 是一种具有口服活性的HDAC抑制剂，IC50值为 0.5-2 mM，抑制HDAC1的活性，(IC50，400 μM)，同时可诱导HDAC2的降解。Valproic acid sodium (2:1) 激活Notch1信号并抑制小细胞肺癌 (SCLC) 细胞的增殖。Valproic acid sodium (2:1) 可用于癫痫、双相情感障碍、代谢疾病、HIV 感染和偏头痛等的研究。
| 生物活性 | Valproic acid (VPA) sodium (2:1) is an orally activeHDACinhibitor, withIC50in the range of 0.5 and 2 mM, also inhibitsHDAC1(IC50, 400 μM), and induces proteasomal degradation ofHDAC2. Valproic acid sodium (2:1) activatesNotch1signaling and inhibits proliferation in small cell lungcancer(SCLC) cells. Valproic acid sodium (2:1) is used in the treatment of epilepsy, bipolar disorder,metabolic disease, HIVinfectionand prevention of migraine headaches[1][2][3][4][5][6][7]. |
| IC50& Target | HDAC1 400 μM (IC50) | HDAC 0.5-2 mM (IC50) | HDAC2 |
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体外研究
(In Vitro) | Valproic acid (VPA) (0-15 mM; 24 and 72 h) inhibits Hela cell growth in a dose- and time- dependent manner[1].
Valproic acid (10 mM; 24 h) significantly attenuates the activities of total, cytosol and nuclear HDACs[1].
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[1].
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[5].
Valproic acid (0-10 mM; 2 days) induces Notch1 signaling and morphologic differentiation, suppresses production of NE tumor markers in SCLC cells[6].
Cell Viability Assay[1] | Cell Line: | HeLa cells | | Concentration: | 0, 1, 3, 5, 10 and 15 mM | | Incubation Time: | 24 and 72 h | | Result: | HeLa cell growth was dose- and time-dependently decreased with an IC50of ~10 and 4 mM at 24 and 72 h. |
Western Blot Analysis[1][2][5] | Cell Line: | HeLa cells, Neuro2A cells or primary mouse hepatocytes | | Concentration: | 10 mM (HeLa); 0, 2, and 5 mM (Neuro2A); 0.2, 0.4, 0.8, 1.2 and 2 mM (hepatocytes) | | Incubation Time: | 24 h (HeLa); 0-18 h (Neuro2A); 0-24 h (hepatocytes) | | Result: | Increased the form of acetylated histone 3.
Reduced PARP, induced cleavage PARP, and downregulated Bcl-2.
Increased β-catenin levels.
Increased the phosphorylation of AMPK and ACC. |
Cell Cycle Analysis[1] | Cell Line: | HeLa cells | | Concentration: | 0, 1, 3, 5, 10 and 15 mM | | Incubation Time: | 24 h | | Result: | Induced a G1 phase arrest at 1–3 mM, significantly induced a G2/M phase arrest at 10 mM, and increased the percentage of sub-G1 cells in HeLa cells in a dose-dependent manner at 24 h. |
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体内研究
(In Vivo) | Valproic acid (VPA) (500 mg/kg; i.p.; daily for 12 days) inhibits tumor angiogenesis in mice transplanted with Kasumi-1 cells[3].
Valproic acid (350 mg/kg; i.p.; once) enhances social behavior in rats[4].
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[5].
| Animal Model: | Female BALB/c nude mice, Kasumi-1 tumor model[3] | | Dosage: | 500 mg/kg | | Administration: | Intraperitoneal injection, daily for 12 days | | Result: | Inhibited tumor growth and tumor angiogenesis.
Inhibited the mRNA and protein expression of VEGF, VEGFR2 and bFGF.
Inhibited HDAC activity and increased acetylation of histone H3.
Enhanced the accumulation of hyperacetylated histone H3 on VEGF promoters. |
| Animal Model: | Timed-pregnant Long Evans rats[4] | | Dosage: | 350 mg/kg | | Administration: | Intraperitoneal injection, once | | Result: | Demonstrated more social investigation and play fighting than control animals. |
| Animal Model: | Obese phenotype of ob/ob mice[5] | | Dosage: | 0.26% (w/v) | | Administration: | Oral via drinking water, 14 days | | Result: | Revealed a marked reduction in the accumulation of fats in the liver as compared with the untreated mice, significantly decreased liver mass to body mass, decreased serum triglyceride concentrations, and did not induce hepatotoxicity. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
