BEGACESTAT

生物活性靶点体内研究 BEGACESTAT 试剂级价格

BEGACESTAT

CAS号:769169-27-9
英文名:Begacestat
中文名:BEGACESTAT
CBNumber:CB72535664
分子式:C9H8ClF6NO3S2
分子量:391.74
MOL File:769169-27-9.mol

BEGACESTAT化学性质

熔点 :153-155°C
沸点 :355℃
密度 :1.642
闪点 :169℃
储存条件 :2-8°C
溶解度 :DMSO: ≥15mg/mL
形态 :powder
酸度系数(pKa) :8.16±0.50(Predicted)
颜色 :white to tan

安全信息

WGK Germany :3

BEGACESTAT性质、用途与生产工艺

生物活性 Begacestat (GSI-953) 是淀粉样前体蛋白 γ 分泌酶 (gamma-secretase) 的选择性噻吩磺酰胺抑制剂 (IC50Aβ40=15 nM)，有潜力用于阿尔兹海默症的研究。
靶点

IC50: 15 nM (Aβ ₄₀ ).

体内研究

Begacestat (5 mg/kg, p.o. in mice) treatment for 4 h significantly reduces the Aβ ₄₀ and Aβ ₄₂ in brain (37% lowering of brain Aβ ₄₀ and 25% lowering of Aβ ₄₀ observed).
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. 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.
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.

Animal Model:	Tg2576 mice
Dosage:	0, 2.5, 5, or 10 mg/kg
Administration:	Oral gavage for two consecutive days
Result:	Resulted in a dose-dependent reversal of contextual fear conditioning deficits when compound is orally administered 3 h before training.

Animal Model:	Sprague-Dawley rats
Dosage:	0, 200, 600, or 2000 mg/kg/day for 10 (5 males/group and 5 females at 600 mg/kg/day) or 28 (10/sex/group) consecutive days
Administration:	P.O. for 10 (5 males/group and 5 females at 600 mg/kg/day) or 28 (10/sex/group) consecutive days.
Result:	A dosage-related trend of slightly lower percentages of SP CD4+ cells in males at all dosages and females at 2000 mg/kg/day was observed.