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.

journal_name

Curr Protein Pept Sci

authors

Wang H,Yang Q,Dou QP,Yang H

doi

10.2174/1389203718666170111121856

subject

Has Abstract

pub_date

2018-02-13 00:00:00

pages

358-367

issue

4

eissn

1389-2037

issn

1875-5550

pii

CPPS-EPUB-80975

journal_volume

19

pub_type

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