Description
LRRK2-IN-1 is a potent and selective inhibitor ofleucine-rich repeat kinase 2 (LRRK2) with IC50 values of 13 nM and 6 nM for wild-type LRRK2 and G2019S mutant LRRK2, respectively.
Product Overview
LRRK2-IN-1 is a potent and selective inhibitor of LRRK2 with IC50 value of 13 nM. 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 Parkinsons disease. The LRRK2 Gly2019Ser mutation is a common cause of familial Parkinsons disease. The Gly2019Ser mutation has been proved to cause Parkinsons disease, even though it is a small number of LRRK2 mutations. LRRK2 also has relationship with Crohns 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. 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.
Molecular Formula
C31H38N8O3
Chemical Name
2-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one
Solubility
Soluble in DMSO > 10 mM
Shipping Conditions
Evaluation sample solution: ship with blue ice. All other available size: ship with RT, or blue ice upon request
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