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Novel enzyme inhibitor paves way for new cancer drug
Date:5/15/2008

(PHILADELPHIA) Combining natural organic atoms with metal complexes, scientists at The Wistar Institute have developed a new type of enzyme inhibitor capable of blocking a biochemical pathway that plays a key role in cancer development.

Based on studies in human melanoma cells, the research paves the way for developing new ways to treat cancer by dampening the overactive enzyme activity that leads to uncontrolled tumor growth.

Details of the study, to be published in the May 16 issue of the journal ACS Chemical Biology, show how small-molecule inhibitors can be designed to target a family of signaling proteins, called phosphatidyl-inositol-3-kinases, or PI3Ks.

The PI3K pathway has been called the most mutated pathway in human cancer, says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and senior author of the study.

PI3Ks are a family of lipid kinases enzymes that transfer a phosphate group to an important signaling molecule in the cell called a lipid. They play a key role in a wide range of cellular functions, including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Lipid kinases also drive cell division by modifying fatty acid molecules and directing cells to grow, change shape and move.

Kinases have been the focus of drug development strategies for years, with some protein kinase-inhibiting compounds, such as Gleevec, already being used clinically to inhibit tumor growth. Though pharmaceutical companies have a keen interest in developing similar types of inhibitors for lipid kinases, targeting these enzymes remains a challenge.

The problem is, the drugs often lack specificity, Marmorstein says. Such broad-spectrum compounds, which inhibit many different but related kinases, inevitably cause side effects and are therefore poor drug candidates. For these reasons, none of the PI3K-inhibitors developed to date
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Contact: Abbey J. Porter
aporter@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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