PT - JOURNAL ARTICLE AU - MICHAEL W. EPPERLY AU - JOSHUA R. SACHER AU - TANJA KRAINZ AU - XIAOLIN ZHANG AU - PETER WIPF AU - MARY LIANG AU - RENEE FISHER AU - SONG LI AU - HONG WANG AU - JOEL S. GREENBERGER TI - Effectiveness of Analogs of the GS-Nitroxide, JP4-039, as Total Body Irradiation Mitigators DP - 2017 Jan 01 TA - In Vivo PG - 39--43 VI - 31 IP - 1 4099 - http://iv.iiarjournals.org/content/31/1/39.short 4100 - http://iv.iiarjournals.org/content/31/1/39.full SO - In Vivo2017 Jan 01; 31 AB - Background/Aim: 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. Materials and Methods: 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. Results: The results demonstrate the superiority of JP4-039 as a systemic radiation mitigator. Conclusion: Structure–activity relationships and bioassays demonstrate that JP4-039 is an optimized small-molecule radiation mitigator.