title: Discovery of Natural Proteasome Inhibitors as Novel Anticancer Therapeutics: Current Status and Perspectives.
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.
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Oncology and Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, Michigan, MI, United States.|Protein Modification and Degradation Lab, School of Basic Medical Sciences, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China.
authors.forename: Huanjie
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D000069286:Bortezomib / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D061988:Proteasome Inhibitors; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex
keywords: Natural compound; cancer; clinical trial.; drug discovery; proteasome inhibitor; ubiquitin proteasome system