Valproic acid (Synonyms: 丙戊酸; VPA; 2-Propylpentanoic Acid)
Valproic acid (VPA) 是一種具有口服活性的 HDAC 抑制劑，IC50 值為 0.5-2 mM，抑制 HDAC1 的活性，(IC50，400 μM)，同時(shí)可誘導(dǎo) HDAC2 的降解。Valproic acid 激huo Notch1 信號(hào)并抑制小細(xì)胞肺ai (SCLC) 細(xì)胞的增殖。Valproic acid 可用于癲癇、雙相情感障礙、代謝疾病、HIV 感ran和偏頭tong等的研究。
生物活性
Valproic acid (VPA) 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 activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid is used in the treatment of epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches[1][2][3][4][5][6][7].
體外研究(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 IC50 of ~10 and 4 mM at 24 and 72 h. |
體內(nèi)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. |
分子量：144.21
Formula：C8H16O2
CAS 號(hào)：99-66-1
中文名稱：丙戊酸；2-丙基戊酸；二丙基乙酸
運(yùn)輸條件：Room temperature in continental US; may vary elsewhere.
儲(chǔ)存方式
| Pure form | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
溶解性數(shù)據(jù)
In Vitro:
DMSO : 100 mg/mL (693.43 mM; Need ultrasonic)
H2O : 1 mg/mL (6.93 mM; Need ultrasonic and warming)
| 濃度溶劑體積質(zhì)量 | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 6.9343 mL | 34.6717 mL | 69.3433 mL |
| 5 mM | 1.3869 mL | 6.9343 mL | 13.8687 mL |
| 10 mM | 0.6934 mL | 3.4672 mL | 6.9343 mL |
請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)月內(nèi)使用，-20°C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)月內(nèi)使用。
以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用； 以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶
- 1.
請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (17.34 mM); Clear solution
- 2.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (17.34 mM); Clear solution
- 3.
請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (17.34 mM); Clear solution
參考文獻(xiàn)
[1]. Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.
[2]. Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.
[3]. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.
[4]. Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.
[5]. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.
[6]. Platta CS, et al. Valproic acid induces Notch1 signaling in small cell lung cancer cells. J Surg Res. 2008 Jul;148(1):31-7.
[7]. Routy JP, et al. Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med. 2012 May;13(5):291-6.
注：產(chǎn)品僅用于科研
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