HG-10-102-01

SKU: orb1220536

Description

HG-10-102-01 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2 IC50 of 20.3 nM).

Key Properties

• CAS Number: 1351758-81-0
• MW: 377.83
• Purity: >98% (HPLC)
• Formula: C₁₇H₂₀ClN₅O₃
• SMILES: CNc1nc(Nc2ccc(cc2OC)C(=O)N2CCOCC2)ncc1Cl
• Target: LRRK2
• Solubility: DMSO:50 mg/mL (132.33 mM)

Bioactivity

• In Vivo:
  HG-10-102-01 (0-100 mg/kg, IP, once) shows inhibition of LRRK2 Ser910/Ser935 phosphorylation in kidney, spleen, and brain of mice. HG-10-102-01 (1 mg/kg, IV; 10 mg/kg, PO; once) shows good oral bioavailability (%F = 67), a short half-life of 0.13 h, and low plasma exposure. Animal model: Wild type male C57BL/6 mice. Dosage: 0, 3, 10, 30, 50, and 100 mg/kg. Administration: IP, once. Result: Showed near complete dephosphorylation of Ser910 and Ser935 of LRRK2 in all tissues including brain at 100 mg/kg and 50 mg/kg, but only partial inhibition in brain at the 30 and 10 mg/kg doses. Animal model: Wild type male C57BL/6 mice. Dosage: 1 mg/kg (IV); 10 mg/kg (PO). Administration: IV, PO; once (Pharmacokinetic Analysis). Result: Pharmacokinetic Parameters of HG-10-102-01 in male C57BL/6 mice.
• In Vitro:
  HG-10-102-01 (0-3 μM, 90 min) substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant. Western blot analysis. Cell line: HEK293 cells, Mouse Swiss 3T3 cells and Mouse embryonic fibroblast cells. Concentration: 0, 0.01, 0.03, 0.1, 0.3, 1, and 3 μM Incubation time: 90 min. Result: Induced a dose-dependent inhibition of Ser910 and Ser935 phosphorylation in both wild-type LRRK2 and LRRK2[G2019S] stably transfected into HEK293 cells. Induced similar dose-dependent Ser910 and Ser935 dephosphorylation of endogenous LRRK2 in mouse Swiss 3T3 cells and mouse embryonic fibroblast cells.

Storage & Handling

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

Quick Database Links

Gene Symbol

LRRK2