[CAS NO. 290315-45-6] BMS299897
PRODUCTS SPECIFICATIONS [290315-45-6]
DESCRIPTION [290315-45-6]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 511.94 |
| Molecular Formula | C24H21ClF3NO4S |
| SMILES | FC1=CC=C(F)C(N([C@@H](C2=C(CCCC(O)=O)C=C(F)C=C2)C)S(C3=CC=C(Cl)C=C3)(=O)=O)=C1 |
Summary
BMS 299897 is a sulfonamide γ-secretase inhibitor with an IC 50 of 7 nM for Aβ production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).
IC50 & Target
IC50: 7 nM (Aβ, in HEK293 cells) [1]
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) [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 Aβ 1-40 in 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 1-42 seeding 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 1-42 and 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 25-35 increases Aβ 1-42 content (+240%) but fails to affect Aβ 1-40 . BMS-299897 blocks the increase in Aβ 1-42 content and decreased Aβ 1-40 levels 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 1-42 content [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 30 mg/mL ( 58.60 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9534 mL | 9.7668 mL | 19.5335 mL |
| 5 mM | 0.3907 mL | 1.9534 mL | 3.9067 mL |
| 10 mM | 0.1953 mL | 0.9767 mL | 1.9534 mL |
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1.
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 d
- [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 Feb 24;10(2):e0118379.
