Available Online: 23 Dec 2025

Covalent BH3-Mimetics and PROTACs Targeting BCL2 Family for Precision Apoptosis Induction

Volume 1

The BCL2 family of proteins serves as a central regulator of mitochondrial outer membrane permeabilization (MOMP) and intrinsic apoptosis, with anti-apoptotic members such as BCL2, BCL-XL, and MCL1 frequently overexpressed in cancers to evade programmed cell death. Traditional BH3 mimetics, like venetoclax and navitoclax, have revolutionized treatment for hematologic malignancies by competitively inhibiting these pro-survival proteins, yet they face challenges including acquired resistance, on-target toxicities and limited efficacy in solid..