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.
Keywords: GS-nitroxide; Oxidative stress; radiation mitigation.
Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.