IPA-3 (2,29- dihydroxy-1,19-dinaphthyldisuifide) is a highly selective, non-ATP-competitive allosteric inhibitor of PAK1 whose hyperactivity has been shown to be closely related with tumorigenesis. IPA-3 prevented Cdc42-induced PAK1 autophosphorylation on T423 and significantly inhibited PAK1 catalytic activity. The inhibitory action of IPA-3 is achieved in part by binding covalently to the regulatory domain of PAK1 which in turn prevented the physical interaction with Cdc42 or other GTPase activators. Increasing data implicates Pak1 in tumorigenesis and metastasis, thus suggesting that IPA-3 could be a novel oncologic therapy.