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GNE-0877

Names

[ CAS No. ]:
1374828-69-9

[ Name ]:
GNE-0877

[Synonym ]:
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

Biological Activity

[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.


[Related Small Molecules]

LRRK2-IN-1 | IKK-16 | MLi-2 | PF-06447475 | GNE7915 | GSK2578215A | GNE-9605 | CZC-54252 | HG-10-102-01 | JH-II-127 | CZC 25146

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
506.3±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C14H16F3N7

[ Molecular Weight ]:
339.319

[ Flash Point ]:
260.0±32.9 °C

[ Exact Mass ]:
339.141937

[ PSA ]:
91.45000

[ LogP ]:
1.51

[ Vapour Pressure ]:
0.0±1.3 mmHg at 25°C

[ Index of Refraction ]:
1.584

[ Storage condition ]:
2-8℃

[ Water Solubility ]:
Practically insoluble (0.061 g/L) (25 ºC)

Related Compounds