产品说明书

CZC-25146

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Chemical Structure| 1191911-26-8 同义名 : -
CAS号 : 1191911-26-8
货号 : A269266
分子式 : C22H25FN6O4S
纯度 : 99%+
分子量 : 488.535
MDL号 : MFCD28160475
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(92.11 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.05mL

0.41mL

0.20mL

10.23mL

2.05mL

1.02mL

20.47mL

4.09mL

2.05mL
参考文献

[1]Ramsden N, Perrin J, 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]Sofia Domingos,et al. Targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of Parkinson's disease. Future Med Chem. 2019 Aug;11(15):1953-1977.

[3]Jinelle M Wint,et al. Lrrk2 modulation of Wnt signaling during zebrafish development. J Neurosci Res. 2020 Oct;98(10):1831-1842.

[4]Nicolas L Dzamko. LRRK2 and the Immune System. Adv Neurobiol. 2017;14:123-143.

[5] 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.

[6]Nicolas Arbez,et al. G2019S-LRRK2 mutation enhances MPTP-linked Parkinsonism in mice. Hum Mol Genet. 2020 Mar 13;29(4):580-590.