10.1021/acs.molpharmaceut.8b00325.s001
Weichao Li
Weichao
Li
Yiqing Zhou
Yiqing
Zhou
Guanghui Tang
Guanghui
Tang
Nai-Kei Wong
Nai-Kei
Wong
Mengquan Yang
Mengquan
Yang
Dan Tan
Dan
Tan
Youli Xiao
Youli
Xiao
Chemoproteomics Reveals the Antiproliferative Potential
of Parkinson’s Disease Kinase Inhibitor LRRK2-IN‑1 by
Targeting PCNA Protein
American Chemical Society
2018
cancer cells
cancer cell death
LRRK 2-IN
cell cycle arrest
Targeting PCNA Protein LRRK 2-IN
2018-07-11 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Chemoproteomics_Reveals_the_Antiproliferative_Potential_of_Parkinson_s_Disease_Kinase_Inhibitor_LRRK2-IN_1_by_Targeting_PCNA_Protein/6854807
LRRK2-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.