"We found definitive proof that IPA-3 fit into and binds to PAK1's autoregulatory domain, the part of the enzyme where it can, essentially, shut itself off when necessary," Peterson says. "Our tests also demonstrate that IPA-3 is highly selective for PAK1, which means that it is less likely it will also turn off other kinases unintentionally."

The idea is not entirely without precedent, the cancer drug Gleevec, for example, is unusually selective for its target by binding to a region outside of the active site that is less common among kinases. By defining the regulatory domain as a useful target for inhibition, however, researchers now have a specific place to look when trying to develop new therapeutics for protein regulation, Peterson says.

According to Peterson, small molecule inhibitors such as IPA-3, are promising tools for drug discovery. While IPA-3 itself might not be a suitable as a drug for use in humans, the molecule could form the conceptual basis of a new targeted therapeutic.

Source: Fox Chase Cancer Center