(1S,2R)-Alicapistat(ABT-957)

立即咨询

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	2221010-57-5
规格:	≥98%

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议

产品介绍

理化性质和储存条件

Molecular Formula: C25H27N3O4;

Molecular Weight: 433.50

In Vitro	(1S,2R)-Alicapistat (ABT-957) exihibits inadequate CNS-penetration concentrations to obtain a pharmacodynamic effect[1]. Calpain 1 (μ-calpain) and 2 (m-calpain) expression in a calcium-dependent manner with μ-molar or m-molar calcium concentrations required for their respective activation, respectively. (1S,2R)-Alicapistat (compound 22) (100 nM) prevents Aβ oligomer-induced deficits in synaptic transmission in rat[2]. (1S,2R)-Alicapistat (compound 22) (385 nM) diplays efficacy with respect to prevention of NMDA-induced neurodegeneration and A-induced synaptic dysfunction[2]. (1S,2R)-Alicapistat (9-21 nM) has the CSF concentrations without reaching the IC50 for calpain inhibition and shows no dose-limiting toxicities (DLTs) in the broad populations studies[3].
In Vivo	(1S,2R)-Alicapistat (ABT-957, compound 22) (iv or po; 1-3 mg/kg) shows moderate mean plasma clearance values (CLp) in mouse, rat, and dog (0.13-1.04 L/hr.kg), while high in monkey (1.98 L/hr.kg). Mean steady-state volume of distribution values (Vss) were moderate in mouse, dog, and monkey (0.64-1.8 L/kg), but higher in rat (3.4 L/kg). The plasma elimination half-life (t1/2) was shortest in dog (1.7 hours), followed by 2.3 hours in monkey and approximately 6.0 hours in mouse and rat. Oral bioavailability (F) values were high in mouse, rat, and dog (>80%), while moderate in monkey (14%)[2].

In Vitro

(1S,2R)-Alicapistat (ABT-957) exihibits inadequate CNS-penetration concentrations to obtain a pharmacodynamic effect[1]. Calpain 1 (μ-calpain) and 2 (m-calpain) expression in a calcium-dependent manner with μ-molar or m-molar calcium concentrations required for their respective activation, respectively. (1S,2R)-Alicapistat (compound 22) (100 nM) prevents Aβ oligomer-induced deficits in synaptic transmission in rat[2]. (1S,2R)-Alicapistat (compound 22) (385 nM) diplays efficacy with respect to prevention of NMDA-induced neurodegeneration and A-induced synaptic dysfunction[2]. (1S,2R)-Alicapistat (9-21 nM) has the CSF concentrations without reaching the IC50 for calpain inhibition and shows no dose-limiting toxicities (DLTs) in the broad populations studies[3].

In Vivo

(1S,2R)-Alicapistat (ABT-957, compound 22) (iv or po; 1-3 mg/kg) shows moderate mean plasma clearance values (CLp) in mouse, rat, and dog (0.13-1.04 L/hr.kg), while high in monkey (1.98 L/hr.kg). Mean steady-state volume of distribution values (Vss) were moderate in mouse, dog, and monkey (0.64-1.8 L/kg), but higher in rat (3.4 L/kg). The plasma elimination half-life (t1/2) was shortest in dog (1.7 hours), followed by 2.3 hours in monkey and approximately 6.0 hours in mouse and rat. Oral bioavailability (F) values were high in mouse, rat, and dog (>80%), while moderate in monkey (14%)[2].