title: Effectiveness of Analogs of the GS-Nitroxide, JP4-039, as Total Body Irradiation Mitigators.
abstract: Mitochondrial-targeted gramicidin S (GS)-nitroxide, JP4-039, has been demonstrated to be a potent radiation mitigator, and safe over a wide dose range. In addition, JP4-039 has organ-specific effectiveness when locally applied.
  
  
  
  We tested the effect of another GS-nitroxide, XJB-5-131, which has more effective mitochondrial localization, and compared these results to those for radiation mitigation against the hematopoietic syndrome, and two analogs of JP4-039, which have the same mitochondrial localization signal, but different chemical payloads: JRS527.084 contains a second nitroxide per molecule, and TK649.030 contains an ester group attached to the nitroxide.
  
  
  
  The results demonstrate the superiority of JP4-039 as a systemic radiation mitigator.
  
  
  
  Structure-activity relationships and bioassays demonstrate that JP4-039 is an optimized small-molecule radiation mitigator.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.|Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sacher
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.|Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Tanja
authors.initials: T
authors.lastname: Krainz
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.|Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.|Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.|Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Mary
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Renee
authors.initials: R
authors.lastname: Fisher
authors.affiliation: School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, U.S.A.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: C544775:JP4-039; D009589:Nitrogen Oxides; D011837:Radiation-Protective Agents
keywords: GS-nitroxide; Oxidative stress; radiation mitigation