Researchers at the Wistar Institute in Philadelphia, PA have developed an enzyme inhibitor that integrates natural organic atoms with metal complexes. Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and senior author of the study explained that the study led to creation of a lipid kinase inhibitor with a metal complex for stronger structural support; such an agent could not be created through pure organic materials. The integration of metal and organic allows the inhibitor to accept a wider range of ligands that increases kinase activity.

The breakthrough in this study is that the inhibitor agent may overcome the common problem with kinase-inhibiting compounds. Typically, these drugs inhibit several different but related kinases, and cause side effects, making them unsuccessful drug candidates. The new inhibitor developed by Wistar offers specificity. The inhibitor agent can be designed to work on signaling proteins known as phosphatidyl-inositol-3-kinases, or PI3Ks. PI3Ks affect cellular functions, including cell growth, proliferation and differentiation. Not all PI3K proteins are associated with cancer. Therefore, an effective drug will target the cancer-related proteins that cause uncontrolled tumor growth and not affect others, with fewer side effects and toxicity.

The experimentation between the Wistar Institute and Eric Meggers, formerly of the University of Pennsylvania, who has previously created organometallic enzyme inhibitors, integrated organic compounds with the metal Ruthenium, changing the inhibitor to become more selective. The compound, called E5, was then tested on various protein kinases and finally on melanoma cell cultures. E5 inhibited the growth of cells and prevented melanoma invasion.
The Wistar Institute focuses on biomedical research specializing in cancer research and vaccine development. The study was published in the May 16 issue of the Journal ACS Chemical Biology. The next step for the researchers will be to improve upon E5 by creating more organometallic compounds that target different PI3ks.

Adapted from materials by The Wistar Institute. More information available at: http://www.wistar.org/

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