title: Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol.
abstract: We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found to reduce radiation-induced body weight loss and lethality in mouse models. Moreover, several PXT analogs appear to exhibit moderate in vivo antiinflammatory activity as well as in vitro immunoenhancing capabilities. These compounds appear to derive their activity through induction of cancer preventive phase 2 enzymes. The studies described herein suggest that coadministration of a PXT-derived agent with cancer chemotherapeutics or radiation therapy may serve to mitigate a range of therapy-associated toxicities.
authors.affiliation: Preclinical Pharmacology Core Facility and Bio-Organic Laboratory, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Huajin
authors.initials: H
authors.lastname: Dong
authors.forename: Xiuguo
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
authors.forename: John
authors.initials: J
authors.lastname: Hartung
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Wilson
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D019610:Cytoprotection / Q000187:drug effects* / Q000528:radiation effects; D053281:Enediynes / Q000737:chemistry / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D008136:Longevity / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology; D005894:Panax / Q000737:chemistry*; D053279:Polyynes / Q000737:chemistry / Q000494:pharmacology*; D015431:Weight Loss / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays; D023041:Xenograft Model Antitumor Assays
chemical_list: D001688:Biological Products; D053281:Enediynes; D005233:Fatty Alcohols; D053279:Polyynes; C057682:panaxytriol; D017239:Paclitaxel; D005472:Fluorouracil