A new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses

Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):e701-7. doi: 10.1016/j.ijrobp.2011.11.038. Epub 2012 Feb 11.


Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721).

Methods and materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension.

Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 μg/g body weight (equivalent to the human amifostine dose of 910 mg/m(2)), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats.

Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy humans in a wide variety of radioprotection settings, including medical radiation, space travel, and nuclear accidents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amifostine / administration & dosage
  • Animals
  • Diamines / administration & dosage*
  • Diamines / adverse effects
  • Diamines / chemistry
  • Diamines / pharmacokinetics
  • Drug Evaluation, Preclinical
  • Female
  • Ferrets
  • Hypotension / chemically induced*
  • Infusions, Intra-Arterial
  • Infusions, Parenteral
  • Injections, Subcutaneous
  • Male
  • Maximum Tolerated Dose
  • Mice
  • Mice, Inbred ICR
  • Nausea / chemically induced*
  • Radiation Injuries, Experimental / prevention & control*
  • Radiation-Protective Agents / administration & dosage*
  • Radiation-Protective Agents / adverse effects
  • Radiation-Protective Agents / chemistry
  • Radiation-Protective Agents / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Sulfhydryl Compounds / administration & dosage*
  • Sulfhydryl Compounds / adverse effects
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacokinetics
  • Vomiting / chemically induced*


  • 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol
  • Diamines
  • Radiation-Protective Agents
  • Sulfhydryl Compounds
  • Amifostine