Cyanide is an archetypal chemical threat. This powerful natural toxic chemical is encountered in many different settings and potential exposures range from industrial accidents to major terrorist attacks. Cyanide has devastating consequences. Higher quantities lead rapidly to seizures, cardiovascular collapse and death, while lower doses are associated with substantial long-term morbidity including debilitating central nervous system injury. Currently available antidotes simply do not match the complexity or scale of the potential mass casualty threat scenarios, and there is an urgent need to develop novel countermeasures.
The major aims of this CounterACT Center of Excellence Grant are:
- To identify novel classes of cyanide countermeasures using unbiased approaches in a validated zebrafish model system.
- To explore in vivo the structure activity relationships (SAR) of these novel countermeasure classes and using medicinal chemistry generate a series of optimized lead compounds.
- To validate these optimized leads in established murine and rabbit models of cyanide toxicity.
