| Identification | Back Directory | [Name]
GNE-9605 | [CAS]
1536200-31-3 | [Synonyms]
CS-1831
GNE-9605
GNE-9605 USP/EP/BP
GNE-9605;GNE9605;GNE 9605
Diazepam-d8 (exempt preparation)
N2-(5-chloro-1-(3-fluoro-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine
rel-N2-[5-Chloro-1-[(3R,4R)-3-fluoro-1-(3-oxetanyl)-4-piperidinyl]-1H-pyrazol-4-yl]-N4-methyl-5-(trifluoromethyl)-2,4-pyrimidinediamine
2,4-Pyrimidinediamine, N2-[5-chloro-1-[(3R,4R)-3-fluoro-1-(3-oxetanyl)-4-piperidinyl]-1H-pyrazol-4-yl]-N4-methyl-5-(trifluoromethyl)-, rel- | [Molecular Formula]
C16H5ClD8N2O | [MDL Number]
MFCD28167997 | [MOL File]
1536200-31-3.mol | [Molecular Weight]
292.79 |
| Chemical Properties | Back Directory | [Boiling point ]
587.9±60.0 °C(Predicted) | [density ]
1.67±0.1 g/cm3(Predicted) | [storage temp. ]
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | [solubility ]
≥22.5 mg/mL in DMSO | [form ]
solid | [pka]
5.04±0.60(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
GNE-9065 is an orally bioavailable and potent inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 18.7 nM).1 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 Ser1292 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. |
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