Study identifies path to safer drugs for heart disease, cancer

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Posted: Tuesday, March 25, 2014 10:38 am

Massachusetts General Hospital investigators found a way to potentially treat conditions ranging from heart attacks to cancer metastasis by providing a structural basis for the design of new, safer integrin inhibitors.

Current drugs designed to inhibit integrin activation have unintended effects in some patients. In their search for more efficient drugs, the investigators focused on extracellular matrix protein called fibronectin, which binds to an integrin called αvβ3. They identified a high-affinity version of FN10, a fibronectin molecule that interacts with αvβ3, that binds more strongly without causing unintended effects. This finding could enable the design of a new generation of integrin inhibitors without the complications.

“Integrins have an intrinsic ability to shape-shift when they switch from an inactive to an active, adhesive state,” senior author M. Amin Arnaout, MD, director of the MGH Leukocyte Biology Program and the Inflammation and Structural Biology Program, was quoted as saying. “Unfortunately, under some circumstances the integrin inhibitors that have been developed to date can inadvertently induce this shape shifting, and use of these drugs have produced serious, sometimes fatal side effects such as excessive bleeding.”

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