1. Academic Validation
  2. Chemoproteomics Reveals the Antiproliferative Potential of Parkinson's Disease Kinase Inhibitor LRRK2-IN-1 by Targeting PCNA Protein

Chemoproteomics Reveals the Antiproliferative Potential of Parkinson's Disease Kinase Inhibitor LRRK2-IN-1 by Targeting PCNA Protein

  • Mol Pharm. 2018 Aug 6;15(8):3252-3259. doi: 10.1021/acs.molpharmaceut.8b00325.
Weichao Li 1 Yiqing Zhou 1 Guanghui Tang 2 Nai-Kei Wong 3 Mengquan Yang 1 4 Dan Tan 5 Youli Xiao 1 4
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences , Chinese Academy of Sciences , Shanghai 200032 , China.
  • 2 School of Chemical Biology and Biotechnology , Peking University Shenzhen Graduate School , Shenzhen 518055 , China.
  • 3 State Key Discipline of Infection Diseases, Shenzhen Third People's Hospital, The Second Affiliated Hospital , Shenzhen University , Shenzhen 518112 , China.
  • 4 University of Chinese Academy of Sciences , Beijing 100039 , China.
  • 5 Ruijin Hospital , Shanghai Jiaotong University School of Medicine , Shanghai 200025 , China.
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.

Keywords

LRRK2-IN-1; PCNA; antiproliferative; chemical proteomics; click chemistry.

Figures
Products