| Description | Avagacestat (BMS-708163) (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2. |
| In vitro | BMS-708163 在抑制Notch处理方面展示出较弱的选择性，其IC50值为193倍。[1] |
| In vivo | 经口给予BMS-708163能显著降低大鼠和狗的大脑、血浆和脑脊液中的Aβ40水平，并可持续一段时间。在狗中，BMS-708163（6个月内每日3 mg/kg剂量）没有显示出剂量限制效应，并且具有高的大脑对血浆比率（2.4）。[1] |
| Cell experiments | BMS-708163 is dissolved in DMSO. The cell viability is assessed using a tetrazolium salt (WST-8)-based colorimetric assay from the Cell Counting Kit 8 (CCK-8). The cells are seeded into 96-well plates at an initial density of 5×103 cells/well and cultured for 24?h, after which the cells are cultured with DMSO, increased concentrations of gefitinib or BMS708163, BIBW2992, or the combination of BMS708163 and BIBW2992 for an additional 48?h. The A450 is measured in a microplate reader after 10?μL of CCK-8 solution is added and incubated for 1?h. The percentage of growth is shown relative to untreated controls. |
| Target activity | γ-secretase (Aβ42):0.27 nM, γ-secretase (Aβ40):0.3 nM |
| Synonyms | BMS-708163 |
| molecular weight | 520.89 |
| Molecular formula | C20H17ClF4N4O4S |
| CAS | 1146699-66-2 |
| Storage | store at low temperature|Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: < 1 mg/mL (insoluble or slightly soluble) DMSO: 96 mg/mL (184.3 mM) |
| References | 1. Gillman KW, et al. Med Chem Lett, 2010, 1 (3), 120–124. |