Leucine-rich repeat kinase 2 (LRRK2) is an enzyme that in humans is encoded by the PARK8 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease (PD)and also Crohn's disease (CD).
Leucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant PD, PARK8, which is originally defined by linkage analysis of a Japanese family. LRRK2 is a complex kinase consisting of LRR, ROC, COR, kinase, and WD40 domains. LRRK2 plays a key role in axonal extension, autophagy, proliferation, and survival of neurons. In addition to neurons, LRRK2 is highly expressed in immune cells such as B cells, macrophages, and microglia. Several studies have demonstrated that LRRK2 is related to inflammatory responses of microglia that could be involved in the development and progression of neurodegeneration.
LRRK2 is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Leucine-rich repeat kinase 2 (LRRK2) represents a promising drug target for treatment and prevention of Parkinson’s disease (PD), because mutations in LRRK2 are the most common cause of Mendelian forms of the disease. PD-associated LRRK2 variants show decreased GTPase and increased kinase activity.
HG-10-102-01 is a potent and selective inhibitor of wild-type LRRK2(IC50=23.3 nM) and the G2019S mutant(IC50=3.2 nM)
IC50 Value: 23.3 nM (WT LRRK2); 3.2 nM (LRRK2 G2019S) [1]
Target: LRRK2
HG-10-102-01 maintains the ability to potently inhibit the biochemical activity of wild-type and G2019S mutant LRRK2.
CZC-25146 is a potent, selective and metabolically stable LRRK2 inhibitor with IC50 of 4.76 nM/6.87 nM for wild type LRRK2 and G2019S LRRK2 respectively.
JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor, with IC50 of 6.6 nM, 2.2 nM ,47.7 nM for LRRK2-wild-type, LRRK2-G2019S, LRRK2-A2016T.
GNE0877 is a highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitor with an IC50 of 3 nM.
CZC-25146 Hcl is a potent, selective and metabolically stable LRRK2 inhibitor with IC50 of 4.76 nM/6.87 nM for wild type LRRK2 and G2019S LRRK2 respectively.
