2. Academic Validation
  3. Small Molecule Functional Converter of B-Cell Lymphoma-2 (Bcl-2) Suppresses Breast Cancer Lung Metastasis

Small Molecule Functional Converter of B-Cell Lymphoma-2 (Bcl-2) Suppresses Breast Cancer Lung Metastasis

  • ACS Pharmacol Transl Sci. 2024 May 1;7(5):1302-1309. doi: 10.1021/acsptsci.3c00360.
Prasad R Kopparapu 1,  Christiane V Löhr 2,  Martin C Pearce 1,  Shanthakumar Tyavanagimatt 1,  Harikrishna Nakshatri 3,  Siva K Kolluri 1 4
Affiliations

Affiliations

  • 1 Cancer Research Laboratory, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331-8580, United States.
  • 2 Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331-4801, United States.
  • 3 Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202-3082, United States.
  • 4 Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, United States.
PMID: 38751629 DOI: 10.1021/acsptsci.3c00360
Abstract

The B-cell lymphoma-2 (Bcl-2) family of proteins plays a vital role in tumorigenesis. Cancer cells utilize the expression of Bcl-2 to evade therapy and develop resistance. Bcl-2 overexpression also causes Cancer cells to be more invasive and metastatic. About 80% of Cancer deaths are due to metastases, and yet targeted therapies for metastatic cancers are scarce. We discovered a small molecule, BFC1103, which changes the conformation of Bcl-2 to convert the antiapoptotic protein to a proapoptotic protein. BFC1103-induced Apoptosis is dependent on the expression levels of Bcl-2, with higher levels causing more Apoptosis. BFC1103 suppressed the growth of breast Cancer lung metastasis. BFC1103 has the potential for further optimization and development for clinical testing in metastatic cancers that express Bcl-2. This study demonstrates a new approach to target Bcl-2 using a small molecule, BFC1103, to suppress metastatic disease.

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