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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Mini-Review Article

Structure-based Drug Design Strategies in the Development of Small Molecule Inhibitors Targeting Bcl-2 Family Proteins

Author(s): Zhe Yin, Donglin Yang, Jun Wang and Yuequan Jiang*

Volume 17, Issue 8, 2020

Page: [943 - 953] Pages: 11

DOI: 10.2174/1570180817666200213114759

open access plus


Proteins of B-cell lymphoma (Bcl-2) family are key regulators of apoptosis and are involved in the pathogenesis of various cancers. Disrupting the interactions between the antiapoptotic and proapoptotic Bcl-2 members is an attractive strategy to reactivate the apoptosis of cancer cells. Structure-based drug design (SBDD) has been successfully applied to the discovery of small molecule inhibitors targeting Bcl-2 proteins in past decades. Up to now, many Bcl-2 inhibitors with different paralogue selectivity profiles have been developed and some were used in clinical trials. This review focused on the recent applications of SBDD strategies in the development of small molecule inhibitors targeting Bcl-2 family proteins.

Keywords: Bcl-2 family proteins, apoptosis, cancer, structure-based drug design strategy, co-crystal structure, small molecule inhibitors.

Graphical Abstract
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