| Title | Chemoproteomics Reveals the Antiproliferative Potential of Parkinson's Disease Kinase Inhibitor LRRK2-IN-1 by Targeting PCNA Protein |
| Authors | Li, Weichao Zhou, Yiqing Tang, Guanghui Wong, Nai-Kei Yang, Mengquan Tan, Dan Xiao, Youli |
| Affiliation | Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Plant Sci, Inst Plant Physiol & Ecol,CAS Key Lab Synthet Bio, Shanghai 200032, Peoples R China. Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen 518055, Peoples R China. Shenzhen Univ, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, State Key Discipline Infect Dis, Shenzhen 518112, Peoples R China. Univ Chinese Acad Sci, Beijing 100039, Peoples R China. Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Plant Sci, Inst Plant Physiol & Ecol,CAS Key Lab Synthet Bio, Shanghai 200032, Peoples R China. Xiao, YL (reprint author), Univ Chinese Acad Sci, Beijing 100039, Peoples R China. |
| Keywords | LRRK2-IN-1 click chemistry chemical proteomics PCNA antiproliferative CELL NUCLEAR ANTIGEN CHEMICAL PROTEOMICS DNA-REPLICATION CANCER-CELLS DISCOVERY REPAIR IDENTIFICATION DESIGN PROBES ACID |
| Issue Date | 2018 |
| Publisher | MOLECULAR PHARMACEUTICS |
| Citation | MOLECULAR PHARMACEUTICS. 2018, 15(8), 3252-3259. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/517927 |
| ISSN | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.8b00325 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 深圳研究生院待认领 |
