• 提示：详情请下载说明书。

• 产品描述： CZC-25146 is a potent and orally active LRRK2 inhibitor with IC50 values of 4.76 nM and 6.87 nM for wild-type LRRK2 and G2019S LRRK2, respectively. CZC-25146 inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2C as well. CZC-25146 prevents mutant LRRK2-induced injury of neurons in vitro. CZC-25146 exhibits relatively favorable pharmacokinetic properties in mice. CZC-25146 can increase normal α-1-antitrypsin (AAT) secretion and reduce inflammatory cytokines. CZC-25146 can be used to research Parkinson's disease and liver diseases

• 靶点： IC50: 4.76 nM (wild-type LRRK2), 6.87 nM (G2019S LRRK2);LRRK2

• 体外研究：
  CZC-25146 (0.01-5 μM; 7 days) does not cause cytotoxicity in human cortical neurons, nor blocking neuronal development. CZC-25146 (0.01-5 μM; 2 days) potently attenuates G2019S LRRK2-mediated toxicity in primary rodent neurons in a concentration-dependent manner with an EC50 of ~100 nM. CZC-25146 (0.06-1000 nM) rescues LRRK2 G2019S-induced neurite defects in primary human neurons in a dose-dependent manner. CZC-25146 (14.3 and 28.6 μM; 48 h) markedly reduces The mutant AAT encoded by the Z allele (ATZ) polymer load and restores AAT secretion in iPSC-Hepatocyte, without compromising cell viability. Cell Cytotoxicity Assay Cell Line: Human cortical neurons Concentration: 0.01, 0.1, 1 and 5 μM Incubation Time: 7 days Result: Did not cause cytotoxicity in human cortical neurons at concentrations below 5 μM over a seven-day treatment in culture, nor did it block neuronal development.

• 体内研究：
  CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice. CZC-25146 (1 mg/kg for i.v.; 5 mg/kg for p.o.; single dosage) exhibits relatively good pharmacokinetic properties and an extensive distribution throughout animal body following intravenous injection into mice. Animal Model: Genetically modified male mice (6 weeks; over expressing human polymeric ATZ) Dosage: 250 mg/kg Administration: p.o.; 14 days Result: Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%.

• 参考文献：
  1. Ramsden N, et al. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons. ACS Chem Biol. 2011 Oct 21;6(10):1021-8. 2. Atashrazm F, et al. LRRK2 inhibitors and their potential in the treatment of Parkinson's disease: current perspectives. Clin Pharmacol. 2016 Oct 20;8:177-189. 3. Deniz Kent, et al. Small molecule screen employing patient-derived iPS hepatocytes identifies LRRK2 as a novel therapeutic target for Alpha1 Antitrypsin Deficiency.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.047 ml	10.235 ml	20.469 ml
  5 mM	0.409 ml	2.047 ml	4.094 ml
  10 mM	0.205 ml	1.023 ml	2.047 ml
  50 mM	0.041 ml	0.205 ml	0.409 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。

输入产品批号：

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 *