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: Hui Wang, Qingzhu Yang, Q Ping Dou, Huanjie Yang
• Journal: Current protein & peptide science (Curr Protein Pept Sci) Vol. 19 Issue 4 Pg. 358-367 (Feb 13 2018) ISSN: 1875-5550 [Electronic] United Arab Emirates
• PMID: 28079010 (Publication Type: Journal Article, Review)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Antineoplastic Agents
• Biological Products
• Proteasome Inhibitors
• Bortezomib
• Proteasome Endopeptidase Complex

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Biological Products (chemistry, pharmacology)
• Bortezomib (therapeutic use)
• Drug Discovery (methods)
• Humans
• Multiple Myeloma (drug therapy)
• Neoplasms (drug therapy)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors (chemistry, pharmacology)
• Structure-Activity Relationship