(1S,2R)-AlicapiSTAT ((1S,2R)-ABT-957) 是一种具有口服活性的人钙激活中性蛋白酶 (calpains 1和2) 的选择性抑制剂，可用于阿尔茨海默病 (AD) 的研究。 AlicapiSTAT 可减轻羰基还原的代谢倾向，对calpain 1的IC50为 395 nM。

(1S,2R)-Alicapistat ((1S,2R)-ABT-957) is an orally active selective inhibitor of human calpains 1 and 2 with the potential application of Alzheimer's disease (AD) [1]. (1S,2R)-Alicapistat mitigates the metabolic liability of carbonyl reduction and inhibits calpain 1 with an IC 50 value of 395 nM [2].

(1S,2R)-Alicapistat shows 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 IC 50 for calpain inhibition and shows no dose-limiting toxicities (DLTs) in the broad populations studies [3].

(1S,2R)-Alicapistat (compound 22) (iv or po; 1-3 mg/kg) exhibits moderate average 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 (t 1/2 ) 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].

2221010-57-5

C25H27N3O4

433.5

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years