GSK2578215A (GSK-2578215A; GSK 2578215A; GSK-2578215 A) is a novel, highly potent and selective LRRK2 kinase inhibitor with anti-PD (Parkinson's disease) activity. It inhibits LRRK2 (G2019S) and LRRK2 (WT) with an IC50 of 8.9 nM and 10.9 nM, respectively.
理化性质和储存条件
| Molecular Weight (MW) | 399.42 |
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| Formula | C24H18FN3O2 |
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| CAS No. | 1285515-21-0 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 79 mg/mL (197.8 mM) |
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| Water: <1 mg/mL |
| Ethanol: <1 mg/mL |
| SMILES | O=C(NC1=CC=CN=C1)C2=CC(C3=CC(F)=NC=C3)=CC=C2OCC4=CC=CC=C4 |
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| Synonyms | GSK-2578215A; GSK 2578215A; GSK2578215A; 2-(benzyloxy)-5-(2-fluoropyridin-4-yl)-N-(pyridin-3-yl)benzamide InChi Key:
WCIGMFCFPXZRMQ-UHFFFAOYSA-N InChi Code:
InChI=1S/C24H18FN3O2/c25-23-14-19(10-12-27-23)18-8-9-22(30-16-17-5-2-1-3-6-17)21(13-18)24(29)28-20-7-4-11-26-15-20/h1-15H,16H2,(H,28,29) |
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实验参考方法
| In Vitro | In vitro activity: GSK2578215A induces a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells, and induces similar dose-dependent Ser910 and Ser935 dephosphorylation of endogenous LRRK2 in mouse Swiss 3T3 cells. In SH-SY5Y cells, GSK2578215A impairs the autophagy flux by altering autophagosome–lysosome fusion, and induces mitophagy though induction of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling.
Kinase Assay: GSK2578215A is a potent and highly selective LRRK2 inhibitor, which exhibits IC50s of around 10 nM against both wild-type LRRK2 and the G2019S mutant. |
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| In Vivo | In vivo, GSK2578215A (100 mg/kg i.p.) inhibits Ser910 and Ser935 phosphorylation in mouse spleen and kidney, but not in brain. |
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| Animal model | Mice |
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| Formulation & Dosage | 100 mg/kg i.p. |
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| References | Bioorg Med Chem Lett. 2012 Sep 1;22(17):5625-9; Cell Death Dis. 2014 Aug 14;5:e1368. |
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