Small molecule and peptide inhibitors of the pro-survival protein Mcl-1

Howell, Lesley and Beekman, Andrew (2016) Small molecule and peptide inhibitors of the pro-survival protein Mcl-1. ChemMedChem, 11 (8). 802–813. ISSN 1860-7179

[img] Microsoft Word (Mcl-1 Review Final Revised Version) - Submitted Version
Download (2MB)
[img]
Preview
PDF (Beekman_et_al-2015-ChemMedChem) - Published Version
Download (1MB) | Preview

Abstract

The ability of protein–protein interactions to regulate cellular processes in both beneficial and detrimental ways has made them obvious drug targets. The Bcl-2 family of proteins undergo a series of protein–protein interactions which regulate the intrinsic cell-death pathway. The pro-survival members of the Bcl-2 family, including Bcl-2, Bcl-xL, and Mcl-1, are commonly overexpressed in a number of human cancers. Effective modulators of members of the Bcl-2 family have been developed and are undergoing clinical trials, but the efficient modulation of Mcl-1 is still not represented in the clinic. In addition, Mcl-1 is a major cause of resistance to radio- and chemotherapies, including inhibitors that target other Bcl-2 family members. Subsequently, the inhibition of Mcl-1 has become of significant interest to the scientific community. This review covers the progress made to date in modulating the activity of Mcl-1, by both stapled peptides and small molecules. The development of peptides as drug candidates, and the advancement of experimental and computational techniques used to discover small molecules are also highlighted.

Item Type: Article
Additional Information: © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: bcl-2,mcl-1,protein–protein interactions,small-molecule inhibitors,stapled peptides
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 05 Jan 2016 15:00
Last Modified: 07 Nov 2020 00:45
URI: https://ueaeprints.uea.ac.uk/id/eprint/56016
DOI: 10.1002/cmdc.201500497

Actions (login required)

View Item View Item