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GSK2578215A

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Chemical Structure| 1285515-21-0 同义名 : -
CAS号 : 1285515-21-0
货号 : A142087
分子式 : C24H18FN3O2
纯度 : 99%+
分子量 : 399.417
MDL号 : MFCD22665702
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(125.18 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：
生物活性
靶点

  • LRRK2

    LRRK2 (WT), IC50:10.9 nM

    LRRK2 (G2019S), IC50:8.9 nM
描述 Leucine-rich repeat kinase 2 (LRRK2)-dependent signaling pathway is associated with familial and sporadic Parkinson’s disease. GSK2578215A is a potent, highly selective LRRK2 kinase inhibitor with IC50 values of 10.9 nM and 8.9 nM against wild-type LRRK2 and mutant LRRK2, respectively. GSK2578215A (0.01 – 1 μM, 90min incubation) dose-dependently inhibited the phosphorylation of Ser910 and Ser935 in HEK293 cells stably expressing wild-type LRRK2 and mutant LRRK2. Similarly, in human lymphoblastoid cells derived from Parkinson’s disease patient homozygous, GSK2578215A (0.01 – 1 μM, 90min incubation) resulted in the dephosphorylation of endogenous LRRK2 at Ser910 and Ser935[3]. In SH-SY5Y cells transfected with GFP-LC3 vector, 12h treatment with 1nM GSK2578215A significantly increased the protein levels of endogenous LC3 and p62 compared to the control cells. In addition, GSK2578215A also increased the number of autophagosomes per cell and induced the accumulation of 4-HNE in SH-SY5Y cells 12h after the treatment[4]. In vivo, intraperitoneal injection of GSK2578215A (100 mg/kg) to wild-type mice caused complete dephosphorylation of LRRK2 Ser910 and Ser935 in kidney and spleen, whereas no inhibition of LRRK2 Ser910 or Ser935 phosphorylation was found in the brain[3].
作用机制 GSK2578215A is a potent, selective cellular inhibitor of LRRK2 kinase activity that binds at the hinge of the ATP site of LRRK2, inducing significant inhibition against wild-type and mutant LRRK2 both in vitro and in vivo[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.52mL

2.50mL

1.25mL

25.04mL

5.01mL

2.50mL
参考文献

[1]Saez-Atienzar S, Bonet-Ponce L, et al. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis. 2014 Aug 14;5:e1368.

[2]Reith AD, Bamborough P, et al. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9.

[3]Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9.

[4]Saez-Atienzar S, Bonet-Ponce L, Blesa JR, Romero FJ, Murphy MP, Jordan J, Galindo MF. The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis. 2014 Aug 14;5(8):e1368.