AS1842856 _Autophagy 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAS1842856Cat. No.: HY-100596CAS No.: 836620-48-5分式: CHFNO分量: 347.38作靶點(diǎn): Autophagy作通路: Autophagy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 : 7.6 mg/mL (21.88 mM; Need ultrasonic and warmi

2、ng)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.8787 mL 14.3935 mL 28.7869 mL5 mM 0.5757 mL 2.8787 mL 5.7574 mL10 mM 0.2879 mL 1.4393 mL 2.8787 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，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AS1842856種特異性的 Foxo1 抑制劑，IC50 為 30 nM，AS1842856 有效抑制噬 (autophagy) 1。AS1842856 通

3、過(guò)抑制 SIRT1 的表達(dá)來(lái)抑制 FoxO1 活性。AS1842856 僅通過(guò)與 FoxO1 結(jié)合降低 FoxO1 的活性，不 響其轉(zhuǎn)錄和蛋質(zhì)表達(dá) 2。IC50 & Target IC50: 30 nM (Foxo1) 1體外研究AS1842856 potently inhibits human Foxo1 transactivation and reduces glucose production through the1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEinhibition of glucose-6 phosphatase an

4、d phosphoenolpyruvate carboxykinase mRNA levels in a rat hepaticcell line 1. After AS1842856 treatment, there is no significant difference in the protein expression of p-FoxO1 and FoxO1 compared with the control group, but the expression of p-Akt is decreased compared withthe control group 2.體內(nèi)研究 Or

5、al administration of AS1842856 to diabetic db/db mice leads to a drastic decrease in fasting plasmaglucose level via the inhibition of hepatic gluconeogenic genes, whereas administration to normal mice hasno effect on the fasting plasma glucose level. Treatment with AS1842856 also suppresses an incr

6、ease inplasma glucose level caused by pyruvate injection in both normal and db/db mice 1.PROTOCOLCell Assay 1 Rat hepatoma Fao cells are cultured in DMEM with 5.5 mM glucose and 10% FBS. Glucose production rateis measured using glucose CII-test reagent. In brief, after 18 h of treatment with either

7、insulin or AS1842856at the indicated concentrations, the cells are ished three times with PBS. The cells are then incubated for 3 hat 37C in 5% CO2 in a glucose production buffer (glucose-free DMEM, pH 7.4, containing 20 mM sodiumpyruvate, without phenol red) 1.MCE has not independently confirmed th

8、e accuracy of these methods. They are for reference only.Animal AS1842856 is dissolved in 6% cyclodextrin for oral administration. Pyruvate or glucose tolerance tests areAdministration 1 performed in male mice aged 7 to 9 weeks. Mice are orally administered either AS1842856 dissolved in 6%cyclodextr

9、in or vehicle (6% cyclodextrin only) at three time points (8 AM, 6 PM, and 8 AM on the secondday). Food is removed after initial dosing and withheld throughout the study (26-h fasting) 1.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) Cancer

10、 Cell. 2019 Apr 15;35(4):677-691 Cell Death Dis. 2019 May; 10(5): 329. FEBS J. 2019 Jul 22. Biosci Rep. 2019 Apr 9. pii: BSR20190112. Gen Comp Endocrinol. 2018 Dec 1;269:33-45.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Nagashima T, et al. Discovery of novel forkhead box O1

11、 inhibitors for treating type 2 diabetes: improvement of fasting glycemia indiabetic db/db mice. Mol Pharmacol. 2010 Nov;78(5):961-70.2. He J, et al. The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt-FoxO1pathway. Biosci Rep. 2019 May 10;39(5). pii: BSR20190112.McePdfHeight2/2 Master of Small Molecules 您邊的抑制劑師www.MedChemECaution: Product has