|N-(2-((5-氟-2-((2-甲氧基-4-吗啉基苯基)氨基)嘧啶-4-基)氨基)苯基)甲磺酰胺|CsnPharm

CAS No.: 1191911-26-8

CZC-25146 Catalog No. CSN17277

Synonyms: CZC-25146

CZC-25146 is a potent LRRK2 inhibitor with IC50 values of 4.76 and 6.87 nM for for wild-type and G2019S mutant LRRK2, respectively. It also inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2.

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400-920-2911

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技术信息

生物活性

描述Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine kinase involved in multiple cellular processes and signaling pathways^[2]. LRRK2 contains multiple protein-protein interacting domains, a GTPase domain, and a kinase domain. LRRK2 is implicated in many cellular processes including vesicular trafficking, autophagy, cytoskeleton dynamics, and Wnt signaling^[3]. LRRK2 is highly expressed in particular immune cells and has been biochemically linked to the intertwined pathways regulating inflammation, mitochondrial function, and autophagy/lysosomal function^[4]. LRRK2 mutations are the most important cause of familial Parkinson's disease, and non-selective inhibitors are protective in rodent disease models. Because of their poor potency and selectivity, the neuroprotective mechanism of these tool compounds has remained elusive so far, and it is still unknown whether selective LRRK2 inhibition can attenuate mutant LRRK2-dependent toxicity in human neurons. CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency^[5]. Cortical neurons from G2019S-LRRK2 mice showed an increased vulnerability to stress insults, compared with neurons overexpressing wild-type WT-LRRK2, or non-transgenic (nTg) neurons. The exposure of LRRK2 transgenic mice to a sub-toxic dose of MPTP resulted in severe motor impairment, selective loss of dopamine neurons and increased astrocyte activation, whereas nTg mice with MPTP exposure showed no deficits^[6].
参考文献

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.0469 mL
- 10.2347 mL
- 20.4694 mL
- 5 mM
- 0.4094 mL
- 2.0469 mL
- 4.0939 mL
- 10 mM
- 0.2047 mL
- 1.0235 mL
- 2.0469 mL

技术信息

CAS号

1191911-26-8

储存条件

粉末: Keep in dark place,Inert atmosphere,Room temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C22H25FN6O4S

运输

蓝冰

分子量

488.54

别名

CZC-25146

溶解度

DMSO	67.0 mg/mL (137.1 mM)
Water	insoluble

动物实验配方

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