product name GNE-0877
Description: GNE-0877 is a novel, highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor with Ki of 0.7 nM. 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).
References: J Med Chem. 2014 Feb 13;57(3):921-36.
339.32
Formula
C14H16F3N7
CAS No.
1374828-69-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 67 mg/mL (197.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GNE-0877 significantly inhibits LRRK2 cellular activity with IC50 of 3 nM, and shows low turnover in human liver microsomes and hepatocytes. Besides, GNE-0877 is also a reversible CYP1A2 inhibitor with IC50 of 0.7 μM. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In vivo, GNE-0877 shows good oral bioavailability and brain penetration. GNE-0877 inhibits in vivo LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation. |
| Animal model | BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation. |
| Formulation & Dosage | Dissolved in 1% methylcellulose in water; 50 mg/kg; i.p. injection |
| References | J Med Chem. 2014 Feb 13;57(3):921-36. |
