丙戊酸鈉作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetValproic acid sodium saltCat. No.: HY-10585ACAS No.: 1069-66-5分式: CHNaO分量: 166.19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(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months

2、-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 48 mg/mL (288.83 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 6.0172 mL 30.0860 mL 60.1721 mL5 mM 1.2034 mL 6.0172 mL 12.0344 mL10 mM 0.6017 mL 3.0086 mL 6.0172 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；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)備液的保存式和

3、期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。BIOLOGICAL ACTIVITY物活性 Valproic acid sodium salt (Sodium Valproate) 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 sodium salt 激活 Notch1 信號(hào)并抑制細(xì)胞肺癌 (SCLC) 細(xì)胞的增殖。Valproic acid sodium salt 可于癲癇、雙相

4、情感障礙和偏頭痛等的研究。IC & Target HDAC1 HDAC HDAC2 Autophagy400 M (IC50) 0.5-2 mM (IC50)Mitophagy體外研究Valproic acid sodium salt (Sodium Valproate) inhibits the growth dose- and time-dependently with an IC50 of appr 10Page 1 of 2 www.MedChemEand 4 mM at 24 and 72 h, respectively. Valproic acid sodium salt sign

5、ificantly attenuates the activities of total, cytosoland nuclear HDACs. Valproic acid sodium salt increases the form of acetylated histone 3 in HeLa cells. Valproic acidsodium salt (1-3 mM) induces a G1 phase arrest, while 10 mM Valproic acid sodium salt significantly induces a G2/Mphase arrest of c

6、ell cycle in HeLa cells. In addition, Valproic acid sodium salt increases the percentage of sub-G1 cellsin HeLa cells in a dose-dependent manner at 24 h1.Valproic acid sodium salt inhibits the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Valproic acid sodiumsalt inhibits the protein express

7、ion of HDAC1, increases histone H3 acetylation, and enhances the accumulation ofhyperacetylated histone H3 on VEGF promoters2.Valproic acid sodium salt treatment results in increased levels of phosphorylated AMPK/ACC in primary mousehepatocytes. Phosphorylation of ACC following Valproic acid sodium

8、salt treatment is AMPK-dependent. Valproic acidsodium salt inhibits the deacetylase activity of both mouse liver nuclear extracts and human recombinant HDAC1while of the metabolites of Valproic acid, only 2-ene-Valproic acid and 4-ene-Valproic acid diminish deacetylaseactivity4.體內(nèi)研究 Valproic acid so

9、dium salt (Sodium Valproate; 500 mg/kg, i.p.) inhibits the tumor growth and angiogenesisin the mice transplanted with Kasumi-1 cells. The IR rate in the Valproic acid sodium salt group is 57.25% at the end of the experiment2.Valproic acid sodium salt (350 mg/kg, i.p.) demonstrates more social invest

10、igation and play fighting than controlanimals3.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 cells in a 60-mm culture dish are incubated with 10 mM Valproic acid for 24 h. The cells are then

11、 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 determine caspase-3, -8 and -9activities. The supernatants are added to each well in 96-well microtit

12、er 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 reader. The activity of caspase-3, -8 and -9 is expressed in arbitraryabsorbance units.MCE has not in

13、dependently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 In brief, 5105 cells are seeded in 96-well microtiter plates for MTT assays. After exposure to the designated doses ofValproic acid for the indicated times, MTT solution 20 mL: 2 mg/mL in phosphate-buffered

14、 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 added to each well to solubilize the formazan crystals. The optical density ismeasured at 570 nm using a microplate reade

15、r.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 splenectomies, the mice receiv wholeAdministration 2 body irradiation with 137Cs at a dose of 4 Gy. At 48-72 h post-irradiat

16、ion, 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 Valproic acid (n=6) and control (n=6) groups. When the tumors are appr 200 mm3 in size at appr10 days post-implantation, 0.

17、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 diameter (a) and theshortest diameter (b) of the tumor are measured every three days, and the tumor volume (TV) is calc

18、ulated 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 following experiments.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2

19、of 3 www.MedChemE戶(hù)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 acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep

20、. 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):740-50.4. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Acti