Figure 1

Glyoxylate identified as cyanide antidote in metabolite screen. (A) Schematic of the screening process for cyanide toxicity antidotes. 5 dpf zebrafish were added 3 per well to 96 well plates in E3 buffered with 20 mM HEPES and treated with 30 µM human metabolite and 10 µM KCN. (B) Metabolic map illustrating the breadth of the screen. Of the ~ 500 human-derived metabolites tested, THF and glyoxylate were the only molecules that yielded 24 h survival in both of the duplicate screens other than hydroxocobalamin, the positive control. (C) Hit efficacy plot denoting compound rescue capability. 2 points were assigned for 3 h touch responsiveness and 50 points were assigned for 24 h survival after each of the 2 screens (e.g., a compound that produces 24 h survival in both screens receives a score of 100, one that produces 3 h touch responsiveness in one and 24 h survival in the other receives a score of 52). Each peak represents one compound and its corresponding efficacy score.