1374828-69-9

1374828-69-9 structure

Name: GNE-0877
Chemical Name: 1H-Pyrazole-1-acetonitrile, α,α,3-trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-
CAS Number: 1374828-69-9
Molecular Formula: C₁₄H₁₆F₃N₇
Molecular Weight: 339.319
Catalog: Biochemical Inhibitor Autophagy lysosome (Autophagy) LRRK2 inhibitor
Create Date: 2019-01-09 15:58:14
Modify Date: 2024-01-07 15:00:46
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 [1]Target: LRRK2Invitrogen 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 themaintenance of chromosomal stability. The in vivo rat clearance for inhibitor GNE0877 was within 2-fold of measured in vitro stability, and good oral bioavailability (88%) was achieved at 50 mg/kg following administration of a methylcellulose/tween (MCT) suspension.

Name	1H-Pyrazole-1-acetonitrile, α,α,3-trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-
Synonyms	1H-Pyrazole-1-acetonitrile, α,α,3-trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]- 2-Methyl-2-(3-methyl-4-{[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino}-1H-pyrazol-1-yl)propanenitrile GNE0877 alpha,alpha,3-Trimethyl-4-[[4-(methylamino)-5-(trifluoromethyl)-2-pyrimidinyl]amino]-1H-pyrazole-1-acetonitrile

Description	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 [1]Target: LRRK2Invitrogen 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 themaintenance of chromosomal stability. The in vivo rat clearance for inhibitor GNE0877 was within 2-fold of measured in vitro stability, and good oral bioavailability (88%) was achieved at 50 mg/kg following administration of a methylcellulose/tween (MCT) suspension.
Related Catalog	Signaling Pathways >> Autophagy >> LRRK2 Research Areas >> Neurological Disease
References	[1]. Estrada AA, et al. Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2014 Feb 13;57(3):921-36.