BMS-299897

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的 γ-分泌酶抑制剂，优先抑制 APP CTF 裂解，IC50 为 7.1 nM。

A potent γ-secretase inhibitor that preferentially inhibits cleavage of the APP CTF cleavage with IC50 of 7.1 nM; 15-fold lower IC50 value for Notch-1 cleavage (IC50=105.9 nM) in vitro; alleviates Aβ1-42 seeding and short-term memory deficits in the Aβ25-35 mouse model of Alzheimer's disease.Alzheimer's Disease Discontinued.

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).

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.

BMS 299897 | BMS299897

Wnt/Notch/Hedgehog

γ-secretase

γ-secretase

Neurological Disease

Alzheimer Disease

290315-45-6

511.941

C24H21ClF3NO4S

>98% (HPLC)

DMSO: ≥ 30 mg/mL

O=C(O)CCCC1=CC(F)=CC=C1[C@H](N(C2=CC(F)=CC=C2F)S(=O)(C3=CC=C(Cl)C=C3)=O)C

Benzenebutanoic acid, 2-[(1R)-1-[[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)amino]ethyl]-5-fluoro-

(-20℃)

With Ice Pack

≥ 2 years