Description
GNE-9065 is an orally bioavailable and potent inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC
50 = 18.7 nM). It is selective for LRRK2 over 178 kinases, inhibiting only TAK1-TAB1 >50% at a concentration of 0.1 μM. GNE-9065 (10 and 50 mg/kg) inhibits LRRK2 Ser
1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S mutation found in families with autosomal Parkinson’s disease.
Uses
GNE-9605 is a potent, orally active, selective Leucine-rich repeat kinase 2 (LRRK2) inhibitor with an IC50 value of 18.7 nM. GNE-9605 inhibits LRRK2 Ser1292 autophosphorylation. GNE-9605 can be used in research of Parkinson's disease (PD) [1].
in vivo
GNE-9605 (10 and 50 mg/kg; i.p.; once) inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein[1].
GNE-9605 (1 mg/kg, p.o.; 0.5 mg/kg, i.v.; once) displays LRRK2 Ki in the biochemical assay of 2 nM as well as a cellular IC50 of 19 nM. GNE-9605 has a total plasma clearance with excellent oral bioavailability[1].
| Animal Model: | BAC transgenic mice expressing human LRRK2 protein[1]. |
| Dosage: | 10 and 50 mg/kg |
| Administration: | Intraperitoneal injection; once |
| Result: | Inhibited LRRK2 Ser1292 autophosphorylation in a dose-dependent manner. |
| Animal Model: | BAC transgenic mice expressing human LRRK2 protein[1]. |
| Dosage: | 1 mg/kg, p.o.; 0.5 mg/kg, i.v. |
| Administration: | Oral administration and intravenous injection; once |
| Result: | Demonstrated a total plasma clearance of 26 mL min-1 kg-1 with excellent oral bioavailability (90%). |
References
[1]. estrada aa, chan bk, baker-glenn c, et al. discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (lrrk2) small molecule inhibitors. j med chem, 2014, 57(3): 921-936.
