Sources for potential exposure to cyanide of both civilians and military personnel include combustion of nitrogenous materials, commercial accidents and the deliberate release of a cyanogenic chemical. The relative ease in obtaining and releasing cyanide means that the risk of cyanide use in a terrorist attack resulting in a mass casualty situation should not be ignored. Rapid intervention is critical for effective medical intervention in cases of cyanide exposure: treatments require a """"""""three minute solution."""""""" The availability of a rapid, IM injectable antidote should meet this requirement. However, there are no such available treatments - the current cyanide antidotes are administered intravenously. Because intravenous administration is time consuming and requires well trained medical personnel mass exposure to cyanide would likely leave many victims untreated. Because IM administration can be performed via an autoinjector and can therefore be done rapidly by minimally trained personnel there is a critical need for a rapid-acting, IM-injectable antidote for the treatment of mass cyanide casualties. In order to address this need we are advancing our preclinical lead, sulfanegen to clinical development. We have previously demonstrated efficacy of sulfanegen in murine, swine and rabbit models of cyanide toxicity. In these models sulfanegen is effective in reversal of cyanide toxicity by intramuscular injection and therefore should meet the three minute solution. We have recently held a pre-IND meeting with the FDA and our goal is to advance this cyanide antagonist to the clinic by validation of animal models, demonstrate efficacy of sulfanegen in these animal models and perform the required GLP pharmacokinetic and safety evaluation required for clinical trials. We will then commence a Phase 1 human safety study while simultaneously performing the required GLP studies for NDA submission under the animal rule. Successful completion of the aims of this project should lead to a clinical countermeasure for cyanide toxicity that will be applicable in all cases of cyanide exposure from individuals to mass casualty settings. PUBLIC HEALTH

Public Health Relevance

We have discovered a novel cyanide antidote that we have named sulfanegen and demonstrated that it is more effective than existing antidotes in models of cyanide toxicity. We will perform the necessary studies to translate this antidote from the bench to the bedside. Successful completion of the goals of this project will therefore result in a clinical antidote that could be useful in the case of a terrorist attack involving cyanide.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-MDCN-J (50))
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Jett, David A
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Moeller, Bryant M; Crankshaw, Daune L; Briggs, Jacquie et al. (2017) In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals. Toxicol Lett 274:64-68
Summerhill, Eleanor M; Hoyle, Gary W; Jordt, Sven-Eric et al. (2017) An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness. Ann Am Thorac Soc 14:1060-1072
Patterson, Steven E; Moeller, Bryant; Nagasawa, Herbert T et al. (2016) Development of sulfanegen for mass cyanide casualties. Ann N Y Acad Sci 1374:202-9
Stutelberg, Michael W; Vinnakota, Chakravarthy V; Mitchell, Brendan L et al. (2014) Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 949-950:94-8
Patterson, Steven E; Monteil, Alexandre R; Cohen, Jonathan F et al. (2013) Cyanide antidotes for mass casualties: water-soluble salts of the dithiane (sulfanegen) from 3-mercaptopyruvate for intramuscular administration. J Med Chem 56:1346-9
Belani, Kumar G; Singh, Harpreet; Beebe, David S et al. (2012) Cyanide toxicity in juvenile pigs and its reversal by a new prodrug, sulfanegen sodium. Anesth Analg 114:956-61
Chan, Adriano; Crankshaw, Daune L; Monteil, Alexandre et al. (2011) The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning. Clin Toxicol (Phila) 49:366-73
Nagasawa, Herbert T; Goon, David J W; Crankshaw, Daune L et al. (2007) Novel, orally effective cyanide antidotes. J Med Chem 50:6462-4
Crankshaw, Daune L; Goon, David J W; Briggs, Jacquie E et al. (2007) A novel paradigm for assessing efficacies of potential antidotes against neurotoxins in mice. Toxicol Lett 175:111-7