JH-II-127

SKU: orb1225960

Description

A potent and selective inhibitor of both wild-type and G2019S mutant LRRK2 with IC50 of 6.6 and 2.2 nM, respectively; also inhibits LRRK2 A2016T with IC50 of 47.7 nM; substantially inhibits Ser910 and Ser935 phosphorylation of both wild-type LRRK2 and G2019S mutant at 0.1-0.3 uM in a variety of cell types; inhibits Ser935 phosphorylation in mouse brain; orally active.Parkinson's Disease Preclinical.

Key Properties

• CAS Number: 1700693-08-8
• MW: 416.8615
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₁ClN₆O₃
• SMILES: ClC1=CNC2=C1C(NC)=NC(NC3=C(OC)C=C(C(N4CCOCC4)=O)C=C3)=N2
• Target: LRRK2
• Solubility: DMSO: ≥ 30 mg/mL

Bioactivity

• In Vivo:
  JH-II-127 (100 mg/kg; i.p.; single) results in near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain. Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice. Animal model: Wild type male C57BL/6 mice. Dosage: 2 mg/kg (for i. v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.). Administration: Intravenous and intraperitoneal injection; oral administration; single. Result: Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose.
• In Vitro:
  JH-II-127 (0.03, 0.1, 0.3, 1, 3 μM; 90 min) inhibits LRRK2 in HEK293 cells. JH-II-127 (0.3, 1, 3 μM; 90 min) inhibits endogenously expressed LRRK2 in mouse Swiss 3T3 cells. Western blot analysis. Cell line: HEK293 cells (expressing GFP-LRRK2, GFP-LRRK2[G2019S], GFP-LRRK2[G2019S + A2016T], and GFP-LRRK2[A2016T], respectively ). Concentration: 0.03, 0.1, 0.3, 1, 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. Inhibited phosphorylation of Ser910 and Ser935 at approximately 0.3 μM for wild-type LRRK2 and LRRK2[G2019S]. Induced dephosphorylation of Ser910 and Ser935 at a concentration of 0.3-1 μM in the drug-resistant LRRK2[A2016T + G2019S] and LRRK2[A2016T] mutants. Western blot analysis. Cell line: Mouse Swiss 3T3 cells. Concentration: 0.03, 0.1, 0.3, 1, 3 μM Incubation time: 90 min. Result: Induced similar dose-dependent Ser935 dephosphorylation of endogenous LRRK2.

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

JH-II-127 | JH-II 127 | JH-II127

Quick Database Links

Gene Symbol

LRRK2