GNE-9605

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GNE-9605

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:	1536200-31-3
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
500mg	电议

产品介绍

GNE-9605 (GNE 9605; GNE9605) is a novel, brain-penetrant, highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor with anti-PD (Parkinson's disease) activity. It inhibits LRRK2 with a Ki and an IC50 of 2 nM and 19 nM, respectively. In human hepatocytes and liver microsomes, GNE-9605 exhibited excellent human metabolic stability.

理化性质和储存条件

Molecular Weight (MW)	449.83
Formula	C17H20ClF4N7O
CAS No.	1536200-31-3
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 89 mg/mL (197.8 mM)
	Water: <1 mg/mL
	Ethanol: 12 mg/mL (26.7 mM)
Other Info	Chemical Name: N2-(5-chloro-1-((3R,4R)-3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine. InChi Key: PUXPEQJKNAWNQA-DGCLKSJQSA-N InChi Code: InChI=1S/C17H20ClF4N7O/c1-23-15-10(17(20,21)22)4-24-16(27-15)26-12-5-25-29(14(12)18)13-2-3-28(6-11(13)19)9-7-30-8-9/h4-5,9,11,13H,2-3,6-8H2,1H3,(H2,23,24,26,27)/t11-,13-/m1/s1 SMILES Code: FC(C1=CN=C(NC2=C(Cl)N([C@H]3[C@H](F)CN(C4COC4)CC3)N=C2)N=C1NC)(F)F
Synonyms	GNE-9605; GNE 9605; GNE9605;

实验参考方法

In Vitro	In vitro activity: GNE-9605 is highly potent against LRRK2 in both biochemical (Ki = 2.0 nM) and cellular (IC50 = 19 nM) assays. In vitro human MDR1 permeability data, GNE-9605 exhibits excellent brain penetration in higher species. Kinase Assay: In rat pharmacokinetic (PK) studies, GNE-9605 exhibited excellent oral bioavailability of 90% and total plasma clearance of 26 mL/min/kg. In bacterial artificial chromosome (BAC) transgenic mice expressing human G2019S LRRK2 protein with the Parkinson’s disease mutation, GNE-9605 (10 or 50 mg/kg) inhibited LRRK2 Ser1292 autophosphorylation with IC50 value of 20 nM in a concentration dependent way. In cynomolgus monkey PK studies, GNE-9605 exhibited excellent brain penetration. Cell Assay: GNE-9605 retained excellent predicted human metabolic stability when assayed in human liver microsomes and hepatocytes. In addition, no reversible or time-dependent inhibition of any of the major CYP isoforms was observed. The demonstrated metabolic stability, brain penetration across multiple species, and selectivity of these inhibitors support their use in preclinical efficacy and safety studies.
In Vivo	In vivo rat PK studies with GNE-9605 (1 mg/kg, p.o.) demonstrates a total plasma clearance of 26 mL/min/kg with excellent oral bioavailability (90%). In BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation, GNE-9605 (10 and 50 mg/kg, i.p.) inhibits in vivo LRRK2 Ser1292 autophosphorylation.
Animal model	G2019S LRRK2 transgenic mice
Formulation & Dosage	Dissolved in 60% NMP; 10, 50 mg/kg; i.p. injection
References	J Med Chem. 2014 Feb 13;57(3):921-36