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  • 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.

Molecular pharmaceutics (2018-07-12)
Weichao Li, Yiqing Zhou, Guanghui Tang, Nai-Kei Wong, Mengquan Yang, Dan Tan, Youli Xiao
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PCNA human, recombinant, expressed in baculovirus infected Sf9 cells, ≥90% (SDS-PAGE), ≥90% (HPLC)
Sigma-Aldrich
Tris(3-hydroxypropyltriazolylmethyl)amine, 95%
Sigma-Aldrich
Tetraethylammonium borohydride, technical, ≥95% (T)