New compound BQU57 developed to block protein aiding cancer growth

A team of researchers from University of Colorado Cancer Center developed a new compound BQU57 to block protein Ral that aids in growth of cancers like pancreatic, prostate, lung, colon and bladder cancers.

The study describing the development of this novel compound was published in the journal Nature in the second week of September 2014. The lead author of the study was Dan Theodorescu, MD, PhD, professor of Urology and Pharmacology.

The Study

Firstly, 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 cavity open.

Secondly, the team shortlisted 88 molecules out of 500000 potential compounds that could have fit into this cavity. Thereafter, they conducted trials on human cancer cells to find one molecule that could block the protein.

The Findings of the Study

The researchers found that some molecules reduced Ral activation in lung cancers. One compound, namely 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.

Importance of the Study

The study is 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.