Novel Bcl-2 Inhibitors Selectively Disrupt the Autophagy-Specific Bcl-2-Beclin 1 Protein-Protein Interaction.

ABSTRACT: Autophagy plays essential roles in a wide variety of physiological processes, such as cellular homeostasis, metabolism, development, differentiation, and immunity. Selective pharmacological modulation of autophagy is considered a valuable potential therapeutic approach to treat diverse human diseases. However, development of such therapies has been greatly impeded by the lack of specific small molecule autophagy modulators. Here, we performed structure-activity relationship studies on a previously discovered weak Bcl-2 inhibitor SW076956, and developed a panel of small molecule compounds that selectively released Bcl-2-mediated inhibition of autophagy-related Beclin 1 compared to apoptosis-related Bax at nanomolar concentration. Our NMR analysis showed that compound 35 directly bind

SUBMITTER: Dong X 

PROVIDER: S-EPMC9465831 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature