GNE-9605

SKU: orb1226132

Description

GNE-9605 is a highly potent, selective, brain penetrant LRRK2 inhibitor with Ki of 2 nM, pLRRK2 IC50 of 19 nM; dispalys excellent selectivity against 178-membered Invitrogen kinase panel, as well as a representative panel of receptors and ion channels; demonstrates robust concentration-dependent inhibition of LRRK2 Ser1292 autophosphorylation (IC50=20 nM) in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation.

Key Properties

• CAS Number: 1536200-31-3
• MW: 449.8336
• Purity: >98% (HPLC)
• Formula: C₁₇H₂₀ClF₄N₇O
• SMILES: FC(C1=CN=C(NC2=C(Cl)N([C@H]3[C@H](F)CN(C4COC4)CC3)N=C2)N=C1NC)(F)F
• Target: LRRK2
• Solubility: DMSO: ≥ 60 mg/mL

Bioactivity

• In Vivo:
  GNE-9605 (10 and 50 mg/kg; i.p.; once) inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein. 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. Animal model: BAC transgenic mice expressing human LRRK2 protein. 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. 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%).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GNE9605 | GNE 9605

Quick Database Links

Gene Symbol

LRRK2