Mapping the target landscape
In the early 1990s a group of scientists wanted to better understand apoptosis. They wondered if this cellular ability to self-destruct could lead to a cancer-fighting medicine. Several proteins help in the apoptotic process, some that cause cell death and some that prevent it. But they had no idea what those proteins looked like, so there was no way to harness them for drug development.
Researchers took BCL-XL, the easiest-to-access protein, and created a picture of it using two high-powered imaging systems – nuclear magnetic resonance spectroscopy and X-ray crystallography.
According to Andrew Petros, Ph.D., senior principal research scientist, AbbVie, who worked on the project later on, the structure “was a novel fold and generated a lot of excitement because at the time it wasn’t clear which of the BCL proteins would be a good oncology target.”
Now they could try to find small molecules that could bind to, and inhibit these BCL proteins on the surface of cancer cells. The objective was to reset the cell-death program within the cancer cells and induce them to commit suicide.