TREATMENT OF SEPTIC SHOCK WITH MERCAPTOALKYLGUANIDINES

Septic shock is a leading cause of mortality, accounting for 200,000 deaths and $10 billion in health care expenditures in the USA per annum. Current treatment regimens are supportive only, as there are no pharmaceuticals which halt or reverse disease progression. A key final common pathway of injury in septic shock is the production of nitric oxide and peroxynitrite. Inotek Corporation is developing a class of compounds, mercaptoalkylquanidines (MAGs), which potently inhibit NO formation and weakly scavenge peroxynitrite. The Specific Aim of the Phase 1 SBIR proposal is to design, synthesize, and quality analogs of the lead MAG compound, S-methyl-mercaptoethylquanidine, in order to achieve a 2-fold increased inhibition of NO formation and a 10-fold increase in peroxynitrite scavenging. Identification of a compound meeting these requirements would demonstrate commercial feasibility. Such an agent would possible represent the first effective treatment for septic shock and justify pre-clinical studies and a Phase 1 clinical trial to be supported by Phase 2 SBIR funding.