4.7 Article

Trends in targeting Bcl-2 anti-apoptotic proteins for cancer treatment

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 232, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114184

Keywords

Bcl-2 anti-apoptotic proteins; Dual targeting BH3 mimetics; Degraders; Antibody-drug conjugates; Cancer treatment

Funding

  1. National Natural Science Foundation of China [82173687]
  2. Liaoning Revitalization Talents Program [XLYC1902089]

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This review focuses on recent advances in the discovery of novel apoptosis inducers targeting Bcl-2 anti-apoptotic proteins, aiming to overcome existing therapeutic limitations, and introduces strategies and advanced technologies in drug design and optimization.
Apoptosis is the major mode of programmed cell death, which conduces to maintain tissue homeostasis, clearance of abnormal cells and development of organisms. Over the past two decades, great progress and significant clinical benefits in cancer treatment have been made by targeting Bcl-2 anti-apoptotic proteins. However, with the deep research of clinic, the therapeutic value of single target inhibitors is restricted due to the limited monotherapy activity, potential and complex drug resistance as well as monotherapy safety. This review focuses on recent advance in discovery of novel apoptosis inducers targeting Bcl-2 anti-apoptotic proteins aiming to overcome existing therapeutic limitations, and introduce the strategies and advanced technologies in the drug design and optimization. (c) 2022 Published by Elsevier Masson SAS.

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