LRRK2-IN-1

- Overview
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    Background
    
    LRRK2-IN-1 is a potent and selective inhibitor of LRRK2 with IC50 value of 13 nM. [1]LRRK2 (Leucine-rich repeat kinase 2) is also known dardarin. LRRK2 belongs to the leucine-rich repeat kinase family. LRRK2 mostly located in the cytoplasm, however, it also associates with outer membrane of the mitochondrial. LRRK2 interacts with parkin at the C-terminal R2 RING finger domain. Parkin interacted with LRRK2 at the COR domain. LRRK2 mutation will induce apoptotic cell death of neuroblastoma cells. Expression of LRRK2 mutants has a close relationship with autosomal dominant Parkinson's disease. The LRRK2 Gly2019Ser mutation is a common cause of familial Parkinson's disease. The Gly2019Ser mutation has been proved to cause Parkinson's disease, even though it is a small number of LRRK2 mutations. LRRK2 also has relationship with Crohn's disease by genomewide association studies.LRRK2-IN-1 dose-dependent inhibit the activity of wild-type and G2019S LRRK2 with IC50 of 0.17 and 0.04μM respectively in HEK293 cells stably expressing GFP tagged wild-type or mutated LRRK2.[2] LRRK2-IN-1 inhibits the activity of both wild-type and G2019S mutant LRRK2 with IC 50 values of 13 nM and 6 nM respectively in vitro enzyme assay with 0.1 mM ATP. LRRK2-IN-1 competed with ATP. LRRK2-IN-1 has a selective profile compared with other 442 diverse kinases and it has no inhibition effect with LRRK1. LRRK2-IN-1 induced endogenous LRRK2 phosphorylation in lymphoblastoid cells. LRRK2-IN-1 also induced Ser910/Ser935 dephosphorylation of LRRK2 in mice kidney at 100 mg/kg.[1]
    
    [1]. Deng X, Dzamko N, Prescott A, Davies P, Liu Q, Yang Q, Lee JD, Patricelli MP, Nomanbhoy TK, Alessi DR et al: Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat Chem Biol, 7(4):203-205.
    [2]. Hermanson SB, Carlson CB, Riddle SM, Zhao J, Vogel KW, Nichols RJ, Bi K: Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. PLoS One, 7(8):e43580.
- Properties
  - Alternative Name
    
    LRRK 2-IN-1; 2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one
    
    CAS Number
    
    1234480-84-2
    
    Molecular Formula
    
    C31H38N8O3
    
    Molecular Weight
    
    570.7
    
    Appearance
    
    A solid
    
    Purity
    
    99.69%
    
    Solubility
    
    ≥28.55 mg/mL in DMSO; insoluble in H2O; ≥57.2 mg/mL in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Chen J, Su P, et al. "Role of LRRK2 in manganese-induced neuroinflammation and microglial autophagy." Biochem Biophys Res Commun. 2018 Mar 25;498(1):171-177. PMID:29408508

LRRK2-IN-1

Background

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