• 产品描述： (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

• 靶点： IC50: 395 nM (human calpain 1);CysteineProtease

• 体外研究：
  (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.

• 体内研究：
  (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%).

• 参考文献：
  1. Lon HK, et al. Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of Alicapistat, a Selective Inhibitor of Human Calpains 1 and 2 for the Treatment of Alzheimer Disease: An Overview of Phase 1 Studies. Clin Pharmacol Drug Dev. 2019 Apr. 8(3):290
  
  2. Jantos K, et al. Discovery of ABT-957: 1-Benzyl-5-oxopyrrolidine-2-carboxamides as selective calpain inhibitors with enhanced metabolic stability. Bioorg Med Chem Lett. 2019 Aug 1. 29(15):1968-1973.
  
  3. Jastaniah A, Gaisina IN, Knopp RC, Thatcher GRJ. Synthesis of α-Ketoamide-Based Stereoselective Calpain-1 Inhibitors as Neuroprotective Agents. ChemMedChem. 2020 Dec 3. 15(23):2280-2285.

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.307 ml	11.534 ml	23.068 ml
  5 mM	0.461 ml	2.307 ml	4.614 ml
  10 mM	0.231 ml	1.153 ml	2.307 ml
  50 mM	0.046 ml	0.231 ml	0.461 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *