Development of sulfanegen for mass cyanide casualties

Ann N Y Acad Sci. 2016 Jun;1374(1):202-9. doi: 10.1111/nyas.13114. Epub 2016 Jun 16.

Abstract

Cyanide is a metabolic poison that inhibits the utilization of oxygen to form ATP. The consequences of acute cyanide exposure are severe; exposure results in loss of consciousness, cardiac and respiratory failure, hypoxic brain injury, and dose-dependent death within minutes to hours. In a mass-casualty scenario, such as an industrial accident or terrorist attack, currently available cyanide antidotes would leave many victims untreated in the short time available for successful administration of a medical countermeasure. This restricted therapeutic window reflects the rate-limiting step of intravenous administration, which requires both time and trained medical personnel. Therefore, there is a need for rapidly acting antidotes that can be quickly administered to large numbers of people. To meet this need, our laboratory is developing sulfanegen, a potential antidote for cyanide poisoning with a novel mechanism based on 3-mercaptopyruvate sulfurtransferase (3-MST) for the detoxification of cyanide. Additionally, sulfanegen can be rapidly administered by intramuscular injection and has shown efficacy in many species of animal models. This article summarizes the journey from concept to clinical leads for this promising cyanide antidote.

Keywords: 3-MST; 3-mercaptopyruvate sulfurtransferase; cyanide antidote; cyanide poisoning; sulfanegen.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyanides / toxicity*
  • Cysteine / analogs & derivatives*
  • Cysteine / chemistry
  • Cysteine / pharmacology
  • Humans
  • Kinetics
  • Mass Casualty Incidents*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology

Substances

  • Cyanides
  • Prodrugs
  • 3-mercaptopyruvic acid
  • Cysteine