BIO-acetoxime-BIA-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBIO-acetoximeCat. No.: HY-15356CAS No.: 667463-85-6Synonyms: BIA分式: CHBrNO分量: 398.21作靶點(diǎn): GSK-3作通路: PI3K/Akt/mTOR; Stem Cell/Wnt儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 20.83 mg/mL (5

2、2.31 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (5.22 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (5.22 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMS

3、O 90% corn oilSolubility: 2.08 mg/mL (5.22 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BIO-acetoxime (BIA)種有效、選擇性的 GSK-3 抑制劑，對(duì) GSK-3/ 的 IC50 值均為 10 nM；BIO-acetoxime 具有抗驚厥和抗感染作。IC50 & Target GSK-3 GSK-3 CDK5/p35 CDK2/cyclin A10 nM (IC50) 10 nM (IC50) 2.4 M (IC50) 4.3 M (IC50)CDK1/cyclin B63 M (IC50)體外研

4、究 BIO-acetoxime (BIA; Compound 13) is a potent and selective GSK-3/ inhibitor, with IC50s of both 10 nM.BIO-acetoxime (BIA) shows weak effect on CDK5/p35 (IC50, 2.4 M), CDK2/cyclin A (IC50, 4.3 M), andCDK1/cyclin B (IC50, 63 M) 1. BIO-acetoxime (BIA) (5 M and 10 M) increases the viability of HSV-1-i

5、nfected cells but shows little effect on morphology and viability of mockin-fected cells. Moreover, BIO-acetoxime (BIA) (0.625, 1.25, 2.5, 5, and 10 M) significantly reduces the release of HSV-1 particles in OC3cells, with an EC50 of 0.68 0.28 M. BIO-acetoxime (BIA) inhibits the expression of HSV-1

6、genes, and maynot affect the nuclear targeting of HSV-1 capsids. In addition, delayed addition of BIO-acetoxime (BIA) alsoinhibits HSV-1 infection 2.體內(nèi)研究 BIO-acetoxime (BIA) shows anticonvulsant effects in the focal pilocarpine rat model at 0.5 mg/kg, and in 6-Hzfully kindled FVB/N mice at 0.5, 2.5,

7、 and 5 mg/kg via i.p. administration 3.PROTOCOLCell Assay 2 OC3 cells are seeded in 3.5- and 6-cm diameter dishes for western blot analysis and RNA isolation,respectively. Cells are mock treated or exposed to HSV-1 at a multiplicity of infection (m.o.i.) of 5 unlessotherwise specified. The glycogen

8、synthase kinase-3 (GSK-3) inhibitor BIO-acetoxime (BIA), is first dissolvedin DMSO to make a stock solution. Medium containing DMSO serves as a solvent control. Cells arepretreated with medium only, medium containing 0.1 % DMSO or BIO-acetoxime (BIA) for 45 min prior tomock or HSV-1 infection. BIO-a

9、cetoxime (BIA) is also present throughout the infection period. To examinethe direct effect on viruses, HSV-1 is treated directly with medium containing 5 M BIO-acetoxime (BIA) for 1h at room temperature. Cell morphology is observed with an inverted microscope 2.MCE has not independently confirmed t

10、he accuracy of these methods. They are for reference only.Animal Mice 3Administration 3 Male FVB/N mice are used to test the anticonvulsant effects of BIO-acetoxime in fully kindled mice. Toachieve the fully kindled state, mice are stimulated at a fixed subconvulsive threshold current twice daily,ex

11、cept the weekends, with a 4 h minimum interval between stimulations. Kindled mice are then stimulated for2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEonly 2 days a week, twice daily to maintain the fully kindled state. Meanwhile nonkindled mice are kept at theoriginal stimulation scheme for maxi

12、mum 1-2 more weeks. The anticonvulsant effect of BIO-acetoxime (BIA)is investigated in the “epileptic” fully kindled mice by stimulating these animals on Monday morning. OnMonday afternoon, the animals are intraperitoneally (i.p.) injected with vehicle, 30 min prior to stimulation. OnTuesday morning

13、, mice are again stimulated. On Tuesday afternoon, mice are injected i.p. with BIO-acetoxime (BIA) and are stimulated 30 min later. Seizure severity is assessed using Racines scale. Thepretreatment scores are compared with the post-treatment scores, obtained after the treatment on Tuesday.To confirm

14、 any observed effects, the experiment is repeated, respecting 1 week of washout. During thiswashout week, all mice are stimulated for 2 days (twice daily) to maintain the kindled state. Compoundtesting during a longer period has not been validated so far. This means that only one dose of BIO-acetoxi

15、mecan be tested in one batch of kindled mice 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Meijer L, et al. GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol. 2003 Dec;10(12):1255-66.2. Hsu MJ, et al. Antiherpetic potential of 6-bromoindirubin-3-acetoxime (BIO-acetoxime) in human oral epithelial cells. Arch Virol. 2013Jun;158(6):1287-96.3. Aourz N, et al. Identification of GSK-3 as a Potential Therapeutic Entry Point for Epil