title: Targeting PAK1.
abstract: 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.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Galina
authors.initials: G
authors.lastname: Semenova
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA jonathan.chernoff@fccc.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
mesh_terms: D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: cancer; protein–serine–threonine kinases; signaling; small molecules; therapeutics