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Discovery of Natural Proteasome Inhibitors as Novel Anticancer Therapeutics: Current Status and Perspectives

[ Vol. 19 , Issue. 4 ]

Author(s):

Hui Wang, Qingzhu Yang, Q. Ping Dou* and Huanjie Yang*   Pages 358 - 367 ( 10 )

Abstract:


Natural products serve as a main resource for drug discovery. The ubiquitin-proteasome system (UPS) is one of the primary intracellular protein degradation systems, which is responsible for the degradation of most short-lived, mis-folded and aged proteins. The proteasome is a validated target for cancer treatment, since cancer cells are more reliant on high levels of proteasome activity to maintain the dynamic protein homeostasis required for enhanced metabolism and unrestricted proliferation. Encouraged by success of bortezomib in the treatment of multiple myeloma, several second-generation proteasome inhibitors have been developed based on natural resources, and are being tested in various clinical settings. In this paper, we reviewed the most widely investigated proteasome inhibitors, including their natural product origins, compound-discovery and optimization, as well as their current status in both preclinical and clinical studies.

Keywords:

Natural compound, ubiquitin proteasome system, proteasome inhibitor, drug discovery, cancer, clinical trial.

Affiliation:

School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, Department of Oncology and Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, MI, School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001

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