Scientists Find Protein that Blocks Cancer Growth
A team of researchers has found a new way to block the activity of a protein that is known to drive cancer growth.
University of Colorado Cancer Center researchers stated that a protein called Ral is linked to the growth and spread of pancreatic, prostate, lung, colon and bladder cancers.
"When you want to keep an alligator from biting you, you can tie its mouth shut. We took another approach - we put a stick in its mouth to hold it open," said Dan Theodorescu, MD, PhD, professor of Urology and Pharmacology, according to a news release.
The researchers set out to find what changes drove inactive Ral protein to become active. They found that inactive Ral protein has a cavity that disappears when the protein is activated. The team wanted a molecule that could act as a "stick" to keep this mouth open.
The team looked at 500,000 potential compounds that could fit into this cavity. They shortlisted 88 molecules and conducted trials on human cancer cells to find one molecule that could block the protein. The researchers found some molecules that reduced Ral activation in lung cancers.
One compound - RBC8 - was the most successful in inactivating the protein in metastasis form. The team then refined their research and produced derivatives of RBC8. One such derivative called BQU57 was more effective than the parent compound in blocking the activity of Ral.
"We still need to optimize these compounds and then characterize these agents for toxicity in several animal species and determine their optimal route of delivery, such as oral or intravenous before moving to the clinic," Theodorescu said in a news release. "But we see this work as a valuable first step in the development of a novel class of therapeutic agents directed at Ral. The concept of targeting sites on proteins that collapse upon activation, and whose collapse is required for activation, could in principle be used to discover drugs aimed at other proteins driving human disease as well."
The study is published in the journal Nature.