GNE0877
Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the neuroscience research community because it is one of the most compelling targets for a potential disease-modifying Parkinson’s disease therapy. GNE-0877 is a highly potent and selective LRRK2 inhibitors.
In vitro: 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) [1].
In vivo: GNE-0877 was evaluated for its ability to inhibit in vivo LRRK2 Ser1292 autophosphorylation using BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation. Using free-drug concentrations, robust concentration-dependent inhibition of Ser1292 autophosphorylation was observed for GNE-0877 [1].
Clinical trials: Currenlty no clinical data are available.
Reference:
[1] Estrada AA, Chan BK, Baker-Glenn C, Beresford A, Burdick DJ, Chambers M, Chen H, Dominguez SL, Dotson J, Drummond J, Flagella M, Fuji R, Gill A, Halladay J, Harris SF, Heffron TP, Kleinheinz T, Lee DW, Le Pichon CE, Liu X, Lyssikatos JP, Medhurst AD, Moffat JG, Nash K, Scearce-Levie K, Sheng Z, Shore DG, Wong S, Zhang S, Zhang X, Zhu H, Sweeney ZK. 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.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 339.32 |
Cas No. | 1374828-69-9 |
Formula | C14H16F3N7 |
Solubility | ≥21 mg/mL in DMSO; ≥20 mg/mL in EtOH; insoluble in H2O |
Chemical Name | 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile |
SDF | Download SDF |
Canonical SMILES | FC(F)(C1=CN=C(N=C1NC)NC2=CN(C(C)(C#N)C)N=C2C)F |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Description | GNE-0877 is a highly potent and selective inhibitor of leucine-rich repeat kinase 2 (LRRK2) with Ki value of 0.7 nM. | |||||
Targets | LRRK2 | |||||
IC50 | Ki=0.7 nM |
Quality Control & MSDS
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Chemical structure
