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BMS 299897
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BMS 299897
CAS No. : 290315-45-6
MCE 站:BMS 299897
产品活性:BMS 299897 是一种磺胺类γ-secretase 抑制剂,作用于稳定过表达淀粉样前体蛋白 (APP) 的HEK293 细胞,抑制Aβ产生,IC50 为 7 nM。
研究领域:Neuronal Signaling | Stem Cell/Wnt
作用靶点:γ-secretase
In Vitro: BMS-299897 reduces the levels of each of the Aβ peptides. At 1 μM, BMS-299897 decreases these peptides to levels ranging from 20 to 50% of the vehicle control. BMS-299897 treatment reduces the portion of QD-BDNF signals moving in the retrograde direction (p=0.0198) with a concomitant increase in the portion of signals moving in the anterograde direction (p=0.0147).
In Vivo: BMS-299897 shows dose- and time-dependent reductions of amyloid β-peptide (Aβ) in brain, cerebrospinal fluid (CSF), and plasma in young transgenic mice, with a correlation between brain and CSF Aβ levels. BMS-299897 reduces both brain and plasma Aβ1-40 in APP-YAC mice and increases brain concentrations of APPcarboxy-terminal fragments, consistent with γ-secretase inhibition. BMS-299897, attenuates this Aβ25-35-induced Aβ1-42 seeding and toxicity. BMS-299897 is administered at 0.1-1 nmol/mouse, concomittantly with Aβ25-35 (9 nmol) in male Swiss mice. After one week, the contents in Aβ1-42 and Aβ1-40, and the levels in lipid peroxidation are analyzed in the mouse hippocampus. Mice are submitted to spontaneous alternation, passive avoidance and object recognition to analyze their short- and long-term memory abilities. Aβ25-35 increases Aβ1-42 content (+240%) but fails to affect Aβ1-40. BMS-299897 blocks the increase in Aβ1-42 content and decreased Aβ1-40 levels significantly. The compound does not affect Aβ25-35-induced increase in hippocampal lipid peroxidation. Behaviorally, BMS-299897 blocks the Aβ25-35-induced deficits in spontaneous alternation or novel object recognition, using a 1 h intertrial time interval. The co-administration of the γ-secretase inhibitor BMS-299897, in the 0.1-1 μmol/mouse dose-range, completely blocks the Aβ25-35-induced increase in Aβ1-42 content.
相关产品:Natural Product Like Compound Library | Bioactive Compound Library Plus | Neuronal Signaling Compound Library | Stem Cell Signaling Compound Library | CNS-Penetrant Compound Library | Anti-Aging Compound Library | Differentiation Inducing Compound Library | Reprogramming Compound Library | Ferroptosis Compound Library | DAPT | YO-01027 | LY-411575 | Compound E | E 2012 | L-685458 | Semagacestat | NGP555 | Sulindac sulfide | Begacestat | Z-Ile-Leu-aldehyde | gamma-secretase modulator 3 | BMS 433796
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