BMS 299897 is a sulfonamideγ-secretaseinhibitor with anIC₅₀of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).

IC50: 7 nM (Aβ, in HEK293 cells)^[1]

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)^[2].

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 Aβ_1-40in APP-YAC mice and increases brain concentrations of APPcarboxy-terminal fragments, consistent with γ-secretase inhibition. BMS-299897, attenuates this Aβ_25-35-induced Aβ_1-42seeding and toxicity. BMS-299897 is administered at 0.1-1 nmol/mouse, concomittantly with Aβ_25-35(9 nmol) in male Swiss mice. After one week, the contents in Aβ_1-42and Aβ_1-40, 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. Aβ_25-35increases Aβ_1-42content (+240%) but fails to affect Aβ_1-40. BMS-299897 blocks the increase in Aβ_1-42content and decreased Aβ_1-40levels significantly. The compound does not affect Aβ_25-35-induced increase in hippocampal lipid peroxidation. Behaviorally, BMS-299897 blocks the Aβ_25-35-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 Aβ_25-35-induced increase in Aβ_1-42content^[1].

511.94

Solid

C₂₄H₂₁ClF₃NO₄S

290315-45-6

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 30 mg/mL(58.60 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (4.88 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.88 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液