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 Target: LRRK2 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. 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.
|Solubility (25°C)||DMSO 150 mg/mL|
Powder -20°C 3 years ; 4°C 2 years
In solvent -80°C 6 months ; -20°C 1 month
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
 Noeen Malik, et al. Eur J Med Chem. Development and biological evaluation of[ 18 F]FMN3PA & [ 18 F]FMN3PU for leucine-rich repeat kinase 2 (LRRK2) in vivo PET imaging
 Isadora Marques Paiva, et al. Prog Neuropsychopharmacol Biol Psychiatry. Inhibition of Lrrk2 reduces ethanol preference in a model of acute exposure in zebrafish
 Anthony A Estrada, et al. J Med Chem. Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors
|Related LRRK2 Products|
EB-42486 is a novel potent and highly selective inhibitor of G2019S-LRRK2 (IC50 < 0.2 nM).
CZC-54252 is a potent and selective LRRK2 inhibitor with IC50s of 1.28 nM and 1.85 nM for human wild type LRRK2 and G2019S LRRK2, respectively.
WAY-333491 is a LRRK2 kinase inhibitor.
HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM).
GNE-7915 tosylate is a potent, selective and brain-penetrant inhibitor of LRRK2 with an IC50 of 9 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.