TY - JOUR T1 - Targeting PAK1 JF - Biochemical Society Transactions JO - Biochem Soc Trans SP - 79 LP - 88 DO - 10.1042/BST20160134 VL - 45 IS - 1 AU - Semenova, Galina AU - Chernoff, Jonathan Y1 - 2017/02/08 UR - http://www.biochemsoctrans.org/content/45/1/79.abstract N2 - p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents. Given the central role of PAK1 in vital signaling pathways, future clinical development of PAK1 inhibitors will require careful investigation of their safety and efficacy.1,4-NHQ, 1,4-naphthohydroquinone; AID, autoinhibitory domain; BAD, Bcl-2-associated death promoter; CRIB, CDC42/RAC1 interactive-binding; ERα, estrogen receptor alpha; FMR1, fragile X mental retardation 1; FXS, Fragile X syndrome; GRB2, growth factor receptor-bound protein 2; hERG, human ether-á-go-go-related gene; IPA-3, inhibitor p21-activated kinase-3; KO, knockout; MAPK, mitogen-activated protein kinase; NF1, neurofibromatosis type 1; NF2, neurofibromatosis type 2; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PAK1, p21-activated kinase 1 ER -