title: Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.
abstract: PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Roth
authors.affiliation: Department of Chemistry, University of Illinois, 261 Roger Adams Laboratory, Box 36-5, 600 S. Mathews Ave., Urbana, IL, 61801, USA. hergenro@illinois.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hergenrother
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000737:chemistry; D001597:Benzylidene Compounds / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D054852:Small Molecule Libraries / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D001597:Benzylidene Compounds; D054852:Small Molecule Libraries; D014508:Urea; D053148:Caspase 3; C005465:benzothiazole; D015032:Zinc