丙戊酸作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetValproic acidCat. No.: HY-10585CAS No.: 99-66-1分式: CHO分量: 144.21作靶點(diǎn): HDAC; Autophagy; Mitophagy; HIV; Notch作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy; Anti-infection; NeuronalSignaling; Stem Cell/Wnt儲存式: Pure form -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (693.43 mM; Need ultrasonic)H2O : 1 mg/mL (6.93 mM; Need ultrasonic and warming)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 6.9343 mL 34.6717 mL 69.3433 mL5 mM 1.3869 mL 6.9343 mL 13.8687 mL10 mM 0.6934 mL 3.4672 mL 6.9343 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍

3、融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時(shí)，請?jiān)?6 個(gè)內(nèi)使，-20C 儲存時(shí)，請?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% T

4、ween-80 45% salineSolubility: 3.25 mg/mL (22.54 mM); Clear solution此案可獲得 3.25 mg/mL (22.54 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 32.5 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.25 mg/mL (22.54 m

5、M); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 3.25 mg/mL (22.54 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 32.5 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 3.25 mg/mL (22.54 mM); Clear solution此案可獲得 3.25 mg/mL (22.54 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。

6、以 1 mL 作液為例，取 100 L 32.5 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Valproic acid (VPA; 2-Propylpentanoic Acid)種 HDAC 抑制劑，IC50 值為 0.5-2 mM，抑制 HDAC1 的活性，(IC50，400 M)，同時(shí)可誘導(dǎo) HDAC2 的降解。Valproic acid 激活 Notch1 信號并抑制細(xì)胞肺癌 (SCLC) 細(xì)胞的增殖。Valproic acid 可于癲癇、雙相情感障礙和偏頭痛等的研究。IC & Target HDAC1 HDAC H

7、DAC2 Autophagy400 M (IC50) 0.5-2 mM (IC50)Mitophagy體外研究 Valproic acid (VPA; 2-Propylpentanoic Acid) inhibits the growth dose- and time-dependently with an IC50 of appr 10and 4 mM at 24 and 72 h, respectively. Valproic acid significantly attenuates the activities of total, cytosol and nuclearHDACs. V

8、alproic acid increases the form of acetylated histone 3 in HeLa cells. Valproic acid (1-3 mM) induces a G1phase arrest, while 10 mM Valproic acid significantly induces a G2/M phase arrest of cell cycle in HeLa cells. Inaddition, Valproic acid increases the percentage of sub-G1 cells in HeLa cells in

9、 a dose-dependent manner at 24 h1.Valproic acid inhibits the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Valproic acid inhibits the proteinexpression of HDAC1, increases histone H3 acetylation, and enhances the accumulation of hyperacetylated histone H3on VEGF promoters2.Valproic acid trea

10、tment results in increased levels of phosphorylated AMPK/ACC in primary mouse hepatocytes.Phosphorylation of ACC following Valproic acid treatment is AMPK-dependent. Valproic acid inhibits the deacetylaseactivity of both mouse liver nuclear extracts and human recombinant HDAC1 while of the metabolit

11、es of Valproicacid, only 2-ene-Valproic acid and 4-ene-Valproic acid diminish deacetylase activity4.體內(nèi)研究 Valproic acid (VPA; 2-Propylpentanoic Acid; 500 mg/kg, i.p.) inhibits the tumor growth and angiogenesisin the micetransplanted with Kasumi-1 cells. The IR rate in the Valproic acid group is 57.25

12、% at the end of the experiment2.Valproic acid (350 mg/kg, i.p.) demonstrates more social investigation and play fighting than control animals3.PROTOCOLKinase Assay 1 The activity of caspase-3, -8 and -9 is assessed using the caspase-3, -8 and -9 colorimetric assay kits, respectively. Inbrief, 1106 c

13、ells in a 60-mm culture dish are incubated with 10 mM Valproic acid for 24 h. The cells are then washedin PBS and suspended in 5 volumes of lysis buffer provided with the kit. Protein concentrations are determined usingthe Bradford method. Supernatants containing 50 g total protein are used to deter

14、mine caspase-3, -8 and -9activities. The supernatants are added to each well in 96-well microtiter plates with DEVD-pNA, IETD-pNA or LEHD-pNA as caspase-3, -8 and -9 substrates and the plates are incubated at 37C for 1 h. The optical density of each wellis measured at 405 nm using a microplate reade

15、r. The activity of caspase-3, -8 and -9 is expressed in arbitraryabsorbance units.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemECell Assay 1 In brief, 5105 cells are seeded in 96-well microtiter plates for MTT assays. After exp

16、osure to the designated doses ofValproic acid for the indicated times, MTT solution 20 mL: 2 mg/mL in phosphate-buffered saline (PBS) is added toeach well of the 96-well plates. The plates are additionally incubated for 3 h at 37C. Medium is withdrawn from theplates by pipetting and 200 mL DMSO is a

17、dded to each well to solubilize the formazan crystals. The optical density ismeasured at 570 nm using a microplate reader.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Splenectomies are performed on the BALB/c nude mice. One week after the sple

18、nectomies, the mice receiv wholeAdministration 2 body irradiation with 137Cs at a dose of 4 Gy. At 48-72 h post-irradiation, the mice are subcutaneously implantedwith Kasumi-1 cells (2107 cells/mouse with 0.15-0.2 mL) in the right axillary region. The mice are randomLy assignedto two groups, the Val

19、proic acid (n=6) and control (n=6) groups. When the tumors are appr 200 mm3 in size at appr10 days post-implantation, 0.2 mL Valproic acid (500 mg/kg body weight) or 0.2 mL saline is injected intraperitoneallyevery day. Valproic acid is dissolved in saline at a concentration of 25 mg/mL. The longest

20、 diameter (a) and theshortest diameter (b) of the tumor are measured every three days, and the tumor volume (TV) is calculated accordingto the following formula: TV=1/2ab2. Following two weeks of injections, the mice are sacrificed by cervicaldislocation and the tumor masses are removed for the foll

21、owing experiments.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Biomaterials. 2018 Dec 6;193:30-46. Lett Drug Des Discover. 2019 Nov.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Han BR, et al. Valproic a

22、cid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.2. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.3. 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 DevNeurosci. 2013 Dec;31(8):740-