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Mount Sinai researchers develop a multi-target approach to treating tumors
Date:6/7/2012

Researchers from Mount Sinai School of Medicine developed a cancer model built in the fruit fly Drosophila, then used it to create a whole new approach to the discovery of cancer treatments. The result is an investigational compound AD80 that precisely targets multiple cancer genes. Tested in mouse models, the drug proved far more effective and less toxic than standard cancer drugs, which generally focus on a single target. This is the first time that whole-animal screening has been used in a rational, step-wise approach to polypharmacology. The study appears online in the journal Nature.

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology focuses on multi-target drugs and has emerged as a new paradigm in drug discovery. The hope is that AD80showing unparalleled effectiveness in fly and mouse modelswill be tested in Phase I clinical trials.

"We've come up with one drug that hits multiple targets through 'rational polypharmacology,' and our approach represents a new concept we believe will have great success in suppressing tumors," said Ross L. Cagan, Ph.D., Professor and Associate Dean at Mount Sinai School of Medicine, and senior author on the study. "Scientists are beginning to recognize that single-target drugs can be problematic. I believe that, within the next five years, we'll see more drugs entering clinical trials that use rational polypharmacology as the basis of drug discovery."

The study represented an unusual collaboration between fly geneticists and medicinal chemists. Typically, scientists use human tumor cell lines to screen for single target anti-cancer drugs. In this project, Dr. Cagan, along with co-authors Tirtha Das, Ph.D, from Mount Sinai and their collaborators Arvin Dar, PhD and Kevan Shokat, Ph.D. from the University of California, San Francisco, used their fly cancer models to screen a large chemical library for novel drug leads that shrunk the tu
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Contact: Mount Sinai Press Office
newsmedia@mssm.edu
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The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

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