Cancer-promoting Enzyme can Be Inhibited by a Molecule

by Rajshri on  April 21, 2008 at 2:59 PM Research News
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Cancer-promoting Enzyme can Be Inhibited by a Molecule
A cancer promoting enzyme called the p21-activated kinase 1 (PAK1) has been successfully inhibited by using a molecule, scientists at Fox Chase Cancer Center have revealed.

The researchers said that a molecule called IPA-3 could shut down PAK1 before the enzyme becomes active.

The said that the molecule, found from a screen of nearly 33,000 small molecules, could serve as a basis for future breast cancer or cancer therapeutics.

"Previous work suggested that hyperactive signaling by PAK1 can contribute to the growth of tumors, but the trick is how to selectively block PAK1 without damaging similar enzymes that are crucial for healthy cellular function," said lead investigator Dr. Jeffrey R. Peterson, an associate member of Fox Chase.

"IPA-3 represents a proof-of-principle, illustrating a new and highly selective approach to targeting PAK1," he added.

He revealed that IPA-3 works by binding to the protein when it is in the closed configuration, which then prevents PAK1 from becoming active.

"It is like when the Steve Irwin would subdue a crocodile, he would tape its jaws closed to keep it from biting. Likewise, IPA-3 latches onto PAK1 in a way that prevents PAK1 from exposing its active site," Peterson says.

The Fox Chase researchers believe that IPA-3 represents a promising new strategy for creating therapeutics that inhibit PAK1 by mimicking the way cellular enzymes self-regulate in real life, but the IPA-3 molecule itself is not suitable as a therapeutic in its current form.

"IPA-3 requires further experimental study and refinement before it could become a working drug for humans," Peterson says.

A report detailing the study appears in the journal Chemistry and Biology.

Source: ANI
RAS/L

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