| Description | BMS 299897 is a sulfonamide γ-secretase inhibitor. It has an IC50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP). |
| In vitro | BMS-299897 (1 μM) 将这些肽降低至载体对照的20至50%。此外，它还减少了向逆向移动的QD-BDNF信号比例（p=0.0198），同时增加了向正向移动的信号比例（p=0.0147）。[2] |
| In vivo | BMS-299897（0.1-1 nmol/只；雄性瑞士小鼠；一周）能够阻断Aβ1-42含量的增加，并显著降低Aβ1-40水平。该化合物对Aβ25-35诱导的海马区脂质过氧化增加无影响。在行为学上，BMS-299897能够阻止Aβ25-35诱导的自发性交替或新奇对象识别能力的缺陷，使用的是1小时的试验间隔。共同给予γ-分泌酶抑制剂BMS-299897，在0.1-1 μmol/只的剂量范围内，完全阻断了Aβ25-35诱导的Aβ1-42含量增加。[1] |
| Target activity | β-Amyloid (HEK293 cells):7 nM, β-Amyloid (HEK293 cells):7 nM |
| molecular weight | 511.94 |
| Molecular formula | C24H21ClF3NO4S |
| CAS | 290315-45-6 |
| Storage | store at low temperature,keep away from direct sunlight|Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 27.0 mg/mL (52.7 mM) |
| References | 1. Meunier J, et al. The γ-secretase inhibitor 2-[(1R)-1-[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl) amino]ethyl-5-fluorobenzenebutanoic acid (BMS-299897) alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease. Eur J Pharmacol. 2013;698(1-3):193-199. 2. Weissmiller AM, et al. A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP. PLoS One. 2015;10(2):e0118379. 3. Zheng M, et al. Studies on the pharmacokinetics and metabolism of a gamma-secretase inhibitor BMS-299897, and exploratory investigation of CYP enzyme induction. Xenobiotica. 2009;39(7):544-555. 4. Xue YJ, et al. Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma and cerebrospinal fluid, followed by high-performance liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal. 2007;43(5):1728-1736. 5. Anderson JJ, et al. Reductions in beta-amyloid concentrations in vivo by the gamma-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol. 2005;69(4):689-698. 6. Zhang D, et al. In vitro and in vivo metabolism of a gamma-secretase inhibitor BMS-299897 and generation of active metabolites in milligram quantities with a microbial bioreactor. Curr Drug Metab. 2006;7(8):883-896. |