BMS-708163 (Avagacestat) is a potent and selective inhibitor for gamma-secretase, especially at inhibiting cleavage of amyloid precursor protein (APP) to form amyloid-ß (Aß)(1-40) (IC50=0.3nM) and Aß(1-42) (0.27nM). BMS-708163 is ??Notch sparing??, with more than 100 folds more selective for APP than for Notch protein (IC50 of 58nM).
BMS-708163 is developed for treating Alzheimer??s disease (AD). Oral administration of BMS-708163 significantly reduced Aß(1-40) levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs [1]. The results of Phase II clinical trial in mild-to-moderate AD patients demonstrated acceptable tolerability at a single-dose range of 0.3 to 800 mg with a biphasic effect on plasma Aß(1-40) [2].
Technical information:
| Chemical Formula: | C20H17ClF4N4O4S | |
| CAS #: | 1146699-66-2 | |
| Molecular Weight: | 520.88 | |
| Purity: | >98% | |
| Appearance: | White | |
| Chemical Name: | (2R)-2-(N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide | |
| Solubility: | Up to 50 mM in DMSO | |
| Synonyms: | BMS-708163, BMS 708163, BMS708163, Avagacestat |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Gillman, KW., et al. Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable ?-Secretase Inhibitor. ACS Med. Chem. Lett., 2010, 1 (3): 120??124 |
| 2. | Tong G., et al., Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral ?-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012 . 34(3):654-67. Pubmed ID: 22381714 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
