产品说明书

GNE-7915

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Chemical Structure| 1351761-44-8 同义名 : -
CAS号 : 1351761-44-8
货号 : A210153
分子式 : C19H21F4N5O3
纯度 : 99%+
分子量 : 443.395
MDL号 : MFCD25977005
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(236.81 mM)，配合低频超声助溶，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：

5% DMSO+30% PEG 300+5% Tween 80+water 3.1 mg/mL

生物活性
靶点

  • LRRK2

    LRRK2, Ki:1 nM

    LRRK2, IC50:9 nM
描述 The LRRK2 gene, which encodes a large, multidomain protein, is involved in Parkinson’s disease pathophysiogenesis. GNE-7915 is a potent, selective and brain-penetrant inhibitor of LRRK2 with IC50 and Ki of 9 and 1 nM, respectively. Cerep receptor profiling, including expanded brain panels, suggested that GNE-7915 inhibited 5-HT2B with >70% inhibition at 10 μM. It was confirmed to be moderately potent 5-HT2B antagonist in in vitro functional assays[3]. When treated with 1 μM GNE‐7915 for 2 h, there was a significant increase of PPR (pair‐pulse ratio). Single‐pulse‐evoked DA (dopamine) release was also enhanced. Thirty‐minute perfusion also increased DA release and the PPR recorded from the same site[4]. Moreover, pretreatment with GNE-7915 for 24 h was able to prevent LRRK2 G2019S-induced mtDNA damage. Most strikingly, exposure to GNE-7915 for 6 h was able to restore mtDNA damage to control levels[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK293 cells Function assay Inhibition of autophosphorylation of LRRK2 in human HEK293 cells, IC50=0.009 μM 22985112
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.26mL

0.45mL

0.23mL

11.28mL

2.26mL

1.13mL

22.55mL

4.51mL

2.26mL
参考文献

[1]Kavanagh ME, Doddareddy MR, Kassiou M. The development of CNS-active LRRK2 inhibitors using property-directed optimisation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3690-6.

[2]Estrada AA, Liu X, et al. Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2012 Nov 26;55(22):9416-33.

[3]Estrada AA, Liu X, Baker-Glenn C, et al. Discovery of highly potent, selective, and brain-penetrable leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2012;55(22):9416-9433

[4]Qin Q, Zhi LT, Li XT, Yue ZY, Li GZ, Zhang H. Effects of LRRK2 Inhibitors on Nigrostriatal Dopaminergic Neurotransmission. CNS Neurosci Ther. 2017;23(2):162-173

[5]Howlett EH, Jensen N, Belmonte F, et al. LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson's disease. Hum Mol Genet. 2017;26(22):4340-4351