| 货号 | 16711-1mg |
| 描述 | γ-Secretase is a protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors and β-amyloid precursor protein (APP), within the transmembrane domain.1,2 Avagacestat is a potent, orally bioavailable inhibitor of γ-secretase that more potently inhibits the cleavage of APP to Aβ40 than signaling through Notch (IC50s = 0.30 and 58 nM, respectively).3 It shows good pharmacokinetics in rats, dogs, and humans and passes the blood-brain barrier, reducing plasma, brain, and cerebrospinal fluid Aβ40 levels.3,4 While suppressing the production of Aβ38, Aβ40, and Aβ42, γ-secretase inhibitors, including avagacestat, increase the level of APP β-C-terminal fragment, both in vitroandin vivo, altering cell function.5 Avagacestat may impact Notch signaling in vivo, although it is generally considered a “Notch-sparing” γ-secretase inhibitor.6 |
| 别名 | BMS 708163; |
| 供应商 | Cayman |
| 应用文献 | |
| 1.Andersson, E.R. and Lendahl, U. Therapeutic modulation of Notch signalling - are we there yet? Nature Reviews.Drug Discovery 13(5), 357-378 (2014). 2.Jurisch-Yaksi, N.,Sannerud, R. and Annaert, W. A fast growing spectrum of biological functions of γ-secretase in development and disease. Biochim Biophys.Acta. 1828(12), 2815-2827 (2013). 3.Gillman, K.W.,Starrett, J.E., Jr.,Parker, M.F., et al. Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable γ-secretase inhibitor. ACS Med.Chem.Lett. 1(3), 120-124 (2010). 4.Albright, C.F.,Dockens, R.C.,Meredith, J.E., Jr., et al. Pharmacodynamics of selective inhibition of γ-secretase by avagacestat. Journal of Pharmacology and Experimental Therapeutics 344(3), 686-695 (2013). 5.Mitani, Y.,Yarimizu, J.,Saita, K., et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. Journal of Neuroscience 32(6), 2037-2050 (2012). 6.Crump, C.J.,Castro, S.V.,Wang, F., et al. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry 51(37), 7209-7211 (2012). | |
| 运输条件 | Room temperature in continental US; may vary elsewhere |
| 存放说明 | -20 |
| 纯度 | ≥98% |
| 计算分子量 | 520.9 |
| 分子式 | C20H17ClF4N4O4S |
| CAS号 | 1146699-66-2 |
| 稳定性 | ≥ 2 years |
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