Development of sulfanegen for mass cyanide casualties.
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.
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Steven E
SE
Patterson
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Bryant
B
Moeller
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Herbert T
HT
Nagasawa
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Robert
R
Vince
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Daune L
DL
Crankshaw
Center for Drug Design, Academic Health Center, the University of Minnesota, Minneapolis, Minnesota.
Jacquie
J
Briggs
Department of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota.
Michael W
MW
Stutelberg
Department of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota.
Chakravarthy V
CV
Vinnakota
Department of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota.
Brian A
BA
Logue
D000818:Animals; D003486:Cyanides / Q000633:toxicity*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D054527:Mass Casualty Incidents; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology
D003486:Cyanides; D011355:Prodrugs; C008366:3-mercaptopyruvic acid; D003545:Cysteine
3-MST; 3-mercaptopyruvate sulfurtransferase; cyanide antidote; cyanide poisoning; sulfanegen