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LDN-22684: A LRRK2 Inhibitor as a Useful Tool for the Study of Parkinson's Disease
The leucine-rich repeat kinase 2 (LRRK2) is a large protein (2527 amino acids) with serine-threonine (Ser/Thr) protein kinase activity and autophosphorylation activity. It is highly expressed in many mammal tissues. Genetic mutations in the G2019S encoding portion of LRRK2 (LRRK2-G2019S) have been frequently detected in patients with Parkinson's disease (PD).1-3) As a result, inhibitors targeting LRRK2 (especially those selective for the G2019S variant) have been increasingly researched recently not only as a treatment for familial PD, but also as a useful tool to study LRRK2 functions. It is reported that LDN-22684 (1) inhibited LRRK2-G2019S and wild-type LRRK2 in the micromolar range.1,3) Therefore, 1 is regarded as a useful tool for the study of PD.
Schematic of LRRK2 protein structure with reported PD pathogenic familial mutations (red).2)
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References
- 1) Small Molecule Kinase Inhibitors for LRRK2 and Their Application to Parkinson's Disease Models
- 2) Chemical Biology of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors
- 3) Development of a mechanism-based high-throughput screen assay for leucine-rich repeat kinase 2-Discovery of LRRK2 inhibitors
