Researchers in the United Kingdom have successfully developed a new family of drugs shown to inhibit the activity of a protein associated with the development of prostate and certain other cancers

This protein is called AMACR (a-methylacyl-CoA racemase). AMACR has been shown to be present in larger quantities in aggressive prostate cancer cells.

Doctors are aware that levels of the AMACR protein and its activity jump by at least tenfold in all prostate cancers. It also shows similar activity in a number of certain other cancers.

This suggests reducing levels of AMACR in prostate cancer cells using genetic techniques makes them less aggressive and lethal. More important, this kind of clinical intervention means prostate cancer cells become more like normal cells.

This research effort has successfully developed a technique that can locate AMACR and monitor its activity. It's also found certain compounds that can target this AMACR's activity in the lab and stop the cancer cells in their tracks.

Until the development of this new technique that accurately locates the AMACR protein, it was difficult to accurately measure AMACR activity. This also meant it became hard to determine the effectiveness of drugs designed to reduce AMACR activity.

Consequently, only a few studies on developing AMACR-targeted drugs had been launched. Those that did, however, didn't systematically investigate the structural features that contribute to the high effectiveness of genetic techniques.

The discovery of this new family of drugs by a research team from the Departments of Pharmacy & Pharmacology and Chemistry at the University of Bath opens a promising avenue for research to develop new therapies to treat a range of cancers.

The new study systematically varied the structure of a feature called a side-chain to identify important structural features required for the highly effective inhibition of AMACR activity. The study published in the journal Bioorganic Chemistry reporting on this development said the work resulted in a 20-fold increase in effectiveness in the drugs compared to those already known such as ibuprofenoyl-CoA.

The reported new drugs were proven to work in a different way to ibuprofenoyl-CoA and similar drugs.

"This study is really significant because it gives detailed information about the structure of these drugs and provides a rational basis for understanding their behavior," Dr. Matthew Lloyd, lead author from the Department of Pharmacy & Pharmacology, said.

"That means that we have some really promising avenues to explore as we work towards developing new treatments against prostate cancer, and other cancers where AMACR is involved. It is also particularly nice that this study provided important training to the next generation of researchers at Bath."

Researchers warned their work is still in its infancy. Furthermore, researchers did admit their work is certainly promising and they look forward to seeing how their research progresses over the coming years.

prostate cancer
Median Survival for Prostate Cancer Metastases Site Mark Dubowski for Duke Health