GNE-0877

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GNE-0877

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	1374828-69-9
规格:	≥98%

包装与价格：

包装	价格(元)
25mg	电议
50mg	电议
100mg	电议
250mg	电议

产品介绍

GNE-0877 (GNE 0877; GNE0877) is a novel, highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor with important biological activity. It inhibits LRRK2 with a Ki of 0.7 nM. GNE-0877 showed significantly enhanced LRRK2 cellular potency (3 nM) and low turnover in human liver microsomes and hepatocytes with no evidence of glucuronidation. Invitrogen kinase-selectivity profiling (188 kinases) of GNE-0877 at 0.1 μM resulted in only four kinases showing greater than 50% inhibition and suggested that GNE-0877 is a highly selective LRRK2 inhibitor. Furthermore, GNE-0877 possessed a 212-fold biochemical-selectivity index over TTK (Ki = 150 nM).

理化性质和储存条件

	Name: GNE-0877 CAS#: 1374828-69-9 Chemical Formula: C14H16F3N7 Exact Mass: 339.14193 Molecular Weight: 339.31895 Elemental Analysis: C, 49.56; H, 4.75; F, 16.80; N, 28.90
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Technical Information	Synonym: GNE 0877; GNE-0877; GNE0877; Chemical Name: 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile . InChi Key: ZPPUMAMZIMPJGP-UHFFFAOYSA-N InChi Code: InChI=1S/C14H16F3N7/c1-8-10(6-24(23-8)13(2,3)7-18)21-12-20-5-9(14(15,16)17)11(19-4)22-12/h5-6H,1-4H3,(H2,19,20,21,22) SMILES Code: CC(N1N=C(C)C(NC2=NC=C(C(F)(F)F)C(NC)=N2)=C1)(C)C#N

实验参考方法

In Vitro	In vitro activity: GNE-0877 significantly inhibits LRRK2 cellular activity with IC50 of 3 nM, and shows low turnover in human liver microsomes and hepatocytes. Besides, GNE-0877 is also a reversible CYP1A2 inhibitor with IC50 of 0.7 μM. Kinase Assay: GNE0877 is a highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitor with an IC50 of 3 nM. IC50 value: 3 nM. Invitrogen kinase-selectivity profiling(188 kinases) of aminopyrazole GNE0877 at 0.1 μM (145-fold overLRRK2 Ki) resulted in only four kinases showing greater than 50% inhibition (Aurora B = 51%, RSK2 = 52%, RSK4 = 62%, and RSK3 = 68%) and suggested that GNE0877 is a highly selective LRRK2 inhibitor. Furthermore, GNE0877 possessed a 212-fold biochemical-selectivity index over TTK (Ki= 150 nM), which was previously highlighted as an off-target kinase of concern because of the suggested role of TTK in the maintenance of chromosomal stability.
In Vivo	In vivo, GNE-0877 shows good oral bioavailability and brain penetration. GNE-0877 inhibits in vivo LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation.
Animal model	BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation.
Formulation & Dosage	Dissolved in 1% methylcellulose in water; 50 mg/kg; i.p. injection
References	J Med Chem. 2014 Feb 13;57(3):921-36.