| Description | Begacestat is a selective thiophene sulfonamide amyloid precursor protein gamma-secretase inhibitor (Aβ40,IC50=15 nM),and for the treatment of Alzheimer's disease. |
| In vivo | Begacestat (GSI-953: 0, 2.5, 5, or 10 mg/kg, oral gavage, 3 h) results in a dose-dependent reversal of contextual fear conditioning deficits when compound is orally administered 3 h before training. Begacestat (5 mg/kg, p.o. in mice) treatment for 4 h significantly reduces the Aβ40 and Aβ42 in brain (37% lowering of brain Aβ40 and 25% lowering of Aβ40 observed)[1]. A dosage-related trend of slightly lower percentages of SP CD4+ cells in males at all dosages (SP CD4+ cells=~11% in controls compared with ~7% to ~9% in Begacestat-dosed animals) and females at 2000 mg/kg/day (SP CD4+ cells=~10% in controls compared with ~8% in Begacestat-dosed animals) is observed[2]. Significant deficits are observed after treatment with 2.5 mg/kg Begacestat, and there is some reversal of this at 5 mg/kg and full reversal at 10 mg/kg compared with vehicle-dosed Tg2576 mice[2]. |
| Target activity | Aβ40:15 nM |
| Synonyms | GSI-953 |
| molecular weight | 391.74 |
| Molecular formula | C9H8ClF6NO3S2 |
| CAS | 769169-27-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Mayer SC, et al. Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease. J Med Chem. 2008 Dec 11;51(23):7348-51. 2. Martone RL, et al. Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease. J Pharmacol Exp Ther. 2009 Nov;331(2):598-608. |