Related Experiment Video
Updated: Jun 18, 2026
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Identification and Characterization of a Small Molecule Bcl-2 Functional Converter
Prasad R Kopparapu1, Martin C Pearce1, Christiane V Löhr2
1Cancer Research Laboratory, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon.
Abstract:
Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2-expressing cancers.
Significance:
We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2-expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.
Insights
Scientists discovered BFC1108, a novel small molecule that targets the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). This molecule converts Bcl-2 into a pro-apoptotic protein, effectively killing cancer cells that overexpress Bcl-2.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cancer cells evade apoptosis by overexpressing the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2).
- High Bcl-2 levels sequester pro-apoptotic proteins, halting the cell death machinery and conferring therapeutic resistance.
Purpose of the Study:
- To discover and characterize a novel small molecule that targets Bcl-2.
- To develop a new therapeutic strategy for Bcl-2-expressing cancers.
Main Methods:
- Identification of the small molecule BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide).
- In vitro and in vivo studies to assess Bcl-2 conformational changes and apoptotic induction.
- Evaluation of BFC1108 efficacy in triple-negative breast cancer xenograft models and metastasis inhibition.
Main Results:
- BFC1108 targets Bcl-2, converting it into a pro-apoptotic protein.
- Bcl-2 overexpression potentiates BFC1108's apoptotic effect.
- BFC1108 induces a Bcl-2 conformational change, exposing its BH3 domain in vitro and in vivo.
- BFC1108 suppressed tumor growth in triple-negative breast cancer xenografts and inhibited lung metastasis.
Conclusions:
- BFC1108 is a novel small molecule Bcl-2 functional converter.
- This molecule effectively induces apoptosis in Bcl-2-expressing cancers, offering a new therapeutic avenue.
Related Concept Videos
01:57Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:31The Intrinsic Apoptotic Pathway