product name GNE-9605
Description: GNE-9605 is a brain-penetrant, highly potent and selective leucine-rich repeat kinase 2 (LRRK2) inhibitor with Ki and IC50 of 2 nM and 19 nM, respectively. In human hepatocytes and liver microsomes, GNE-9605 exhibited excellent human metabolic stability. Leucine-rich repeat kinase 2 (LRRK2) is a member of the leucine-rich repeat kinase family. Variants of LRRK2 gene are the most common cause of Parkinsons disease and Crohns disease.
References: J Med Chem. 2014 Feb 13;57(3):921-36.
449.83
Formula
C17H20ClF4N7O
CAS No.
1536200-31-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 89 mg/mL (197.8 mM)
Water: <1 mg/mL
Ethanol: 12 mg/mL (26.7 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GNE-9605 is highly potent against LRRK2 in both biochemical (Ki = 2.0 nM) and cellular (IC50 = 19 nM) assays. In vitro human MDR1 permeability data, GNE-9605 exhibits excellent brain penetration in higher species. Kinase Assay: In rat pharmacokinetic (PK) studies, GNE-9605 exhibited excellent oral bioavailability of 90% and total plasma clearance of 26 mL/min/kg. In bacterial artificial chromosome (BAC) transgenic mice expressing human G2019S LRRK2 protein with the Parkinson’s disease mutation, GNE-9605 (10 or 50 mg/kg) inhibited LRRK2 Ser1292 autophosphorylation with IC50 value of 20 nM in a concentration dependent way. In cynomolgus monkey PK studies, GNE-9605 exhibited excellent brain penetration. Cell Assay: |
|---|---|
| In Vivo | In vivo rat PK studies with GNE-9605 (1 mg/kg, p.o.) demonstrates a total plasma clearance of 26 mL/min/kg with excellent oral bioavailability (90%). In BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation, GNE-9605 (10 and 50 mg/kg, i.p.) inhibits in vivo LRRK2 Ser1292 autophosphorylation. |
| Animal model | G2019S LRRK2 transgenic mice |
| Formulation & Dosage | Dissolved in 60% NMP; 10, 50 mg/kg; i.p. injection |
| References | J Med Chem. 2014 Feb 13;57(3):921-36 |
