(1S,2R)-Alicapistat

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

(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，可能用于阿尔茨海默病 (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 for the potential application of Alzheimer's disease (AD). (1S,2R)-Alicapistat mitigates the metabolic liability of carbonyl reduction and inhibits calpain 1 with an IC50 value of 395 nM.

(1S,2R)-Alicapistat exihibits inadequate CNS-penetration concentrations to obtain a pharmacodynamic effect.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.(1S,2R)-Alicapistat (compound 22) (385 nM) diplays efficacy with respect to prevention of NMDA-induced neurodegeneration and A-induced synaptic dysfunction.(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.

(1S,2R)-Alicapistat (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%).

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Proteasome/Ubiquitin

Cysteine Protease

Cysteine Protease

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2221010-57-5

433.5

C25H27N3O4

>98% (HPLC)

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O=C(N[C@@H](Cc1ccccc1)C(=O)C(=O)NC1CC1)[C@H]1CCC(=O)N1Cc1ccccc1

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(-20℃)

With Ice Pack

≥ 2 years