An experimental compound, ABT-737, that blocks the action of a class of proteins known as the Bcl-2 family, may prove to be a valuable tool in the fight against cancer.

The Bcl-2 family of proteins plays a central role in regulating apoptosis and, consequently, in tumor formation, tumor growth and resistance to treatment.
These proteins are often overexpressed in solid tumors. Researchers have been interested in the Bcl-2 proteins since their role in preventing apoptosis was proven more than a decade ago.
Pioneering work in structural biology at Abbott established how the Bcl-2 family of proteins interacts with one another.

This protein-protein interaction involves a large surface area and has presented significant difficulty in identifying a small-molecule candidate that would potently inhibit the function of these proteins.
Using SAR by NMR ( structure-activity relationships by nuclear magnetic resonance ), a proprietary technology developed by an Abbott team led by the head of Cancer Research, Stephen Fesik, as well as other methods, Abbott researchers created three-dimensional maps of these intricate proteins and discovered small molecules that bound tightly to the Bcl-2 family of proteins and demonstrated greater potency than any previously discovered compounds.

The data show that ABT-737 binds to the Bcl-2 proteins, and, in effect, restores cell death to cancerous cells.
ABT-737 was found to effectively kill certain cancer cell lines, including lymphoma and small cell lung carcinoma.
Additionally, Abbott Bcl-2 family inhibitors were found to enhance the effects of chemotherapy and radiation in other types of cancer, such as non-small cell lung cancer.

These discoveries are the result of a scientific collaboration between Abbott and Idun Pharmaceuticals focused on developing small-molecule treatments for cancer specifically targeting the apoptotic pathway.

Source: Abbott, 2005


XagenaMedicine2005