IPA-3 (42521-82-4) is a selective allosteric inhibitor of Group 1 p21-activated kinase (PAK1 IC50 = 2.5 µM)1 via covalent binding to the PAK1 regulatory domain preventing binding to the upstream activator Cdc422. IPA-3 has been shown to induce cell death in human leukemic cell lines3, significantly inhibit TGFβ1-induced prostate cell epithelial to mesenchymal transition4 and inhibit the growth of liver cancer cells5.
1) Deacon et al. (2008) An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase; Chem.Biol., 14 322
2) Viaud and Peterson (2009) An allosteric kinase inhibitor binds the p21-activated kinase (PAK) autoregulatory domain covalently; Mol. Cancer Ther., 8 2559
3) Kuzelova et al. (2014) Group 1 PAK Inhibitor IPA-3 Induces Cell Death and Affects Cell Adhesivity to Fibronectin in Human Hematopoietic Cells; PLoS One, 9 e92560
4) Al-Azayzih et al. (2015) P21 Activated Kinase-1 Mediates Transforming Growth factor b1-Induced Prostate Cancer Cell Epithelial to Mesenchymal transition; Biochim. Biophys. Acta, 1853 1229
5) Wong et al. (2013) IPA-3 Inhibits the Growth of Liver Cancer Cells By Suppressing PAK1 and NF-kB Activation; PLoS One, 8 e68843