Avagacestat (BMS-708163) is a potent inhibitor of γ-secretase, with IC₅₀s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; Avagacestat (BMS-708163) also inhibits NICD (Notch IntraCellular Domain) with IC₅₀ of 0.84 nM and shows weak inhibition of CYP2C19, with IC₅₀ of 20 μM. Avagacestat can be used for Alzheimer disease research.

Solid

IC50: 0.27 nM (γ-secretase, Aβ42), 0.30 nM (γ-secretase, Aβ40), 20 μM (CYP2C19), 0.84 nM (NICD)

Avagacestat (BMS-708163) exhibits weaker potency for inhibition of Notch processing, IC₅₀=58±23 nM, as compared to its inhibition potency for APP cleavage. Avagacestat (BMS-708163) (10?μM) combined with gefitinib significantly attenuates the colony growth of PC9/AB2 cells, increases the expression of active caspase 3 and PARP and reduces the expression of Ki-67 in PC9/AB2 cells. Avagacestat (BMS-708163) induces apoptosis and enhances cell cycle arrest at the G1 phase in PC9/AB2 cells. Avagacestat (BMS-708163) treatment effectively downregulates the expression of Notch1, HES1, PI3K and Akt in PC9/AB2 cells.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Avagacestat (BMS-708163) significantly reduces both plasma and brain Aβ40 levels relative to control at 10 and 100 mg/kg for the entire dosing interval, demonstrates significant Aβ40 lowering for 8 h after an oral dose of 1 mg/kg, and significantly lowers CSF Aβ40 levels in rats, when measured 5 h after single oral doses ranging from 3 to 100 mg/kg. Avagacestat (BMS-708163) (10?mg/kg) monotherapy has a minor inhibitory effect on PC9/AB2 tumor growth compared with gefitinib alone. BMS-708163 monotherapy results in a slight increase in caspase 3 expression as well as a mild decrease in Ki-67 expression in vivo. In the xenograft lung cancer samples treated with Avagacestat (BMS-708163) plus gefitinib, there are a marked increase in caspase 3 expression and a reduction in Ki-67 staining.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature or refrigerated transportation.

• [1]. Gillman KW, et al. Letter Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor. Med Chem Lett, 2010, 1 (3), 120-124.  [Information]

  [2]. Xie M, et al. γ Secretase inhibitor BMS-708163 reverses resistance to EGFR inhibitor via the PI3K/Akt pathway in lung cancer. J Cell Biochem. 2015 Jun;116(6):1019-27.  [Information]

  [3]. Crump CJ, et al. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry. 2012 Sep 18;51(37):7209-11.  [Information]

  [4]. Borghys H, et al. A canine model to evaluate efficacy and safety of γ-secretase inhibitors and modulators. J Alzheimers Dis. 2012;28(4):809-22.  [Information]

  [5]. Vladimir Coric, et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.  [Information]

产品不同，其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液；配成溶液后，建议分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，建议在 6 个月内使用，-20°C 储存时，建议在 1 个月内使用。