mp8b00325_si_001.pdf (3.47 MB)
Chemoproteomics Reveals the Antiproliferative Potential of Parkinson’s Disease Kinase Inhibitor LRRK2-IN‑1 by Targeting PCNA Protein
journal contribution
posted on 2018-07-11, 00:00 authored by Weichao Li, Yiqing Zhou, Guanghui Tang, Nai-Kei Wong, Mengquan Yang, Dan Tan, Youli XiaoLRRK2-IN-1,
one of the first selective inhibitors of leucine-rich
repeat kinase 2 (LRRK2), was serendipitously found to exhibit potent
antiproliferative activity in several types of human cancer cells.
In this study, we employed a chemoproteomic strategy utilizing a photoaffinity
probe to identify the cellular target(s) of LRRK2-IN-1 underlying
its anticancer activity. LRRK2-IN-1 was found to induce cell cycle
arrest as well as cancer cell death by specifically binding to human
proliferating cell nuclear antigen (PCNA) in cancer cells. Our current
findings suggest the potential of LRRK2-IN-1 as a novel pharmacological
molecule for scrutinizing cell physiology and furnish a logical foundation
for the future development of therapeutic reagents for cancer.