On H2S Prodrugs.

This Forum was conceived as a means to usher in the age of H2S-based therapeutics and H2S-aided regenerative medicine. H2S prodrugs-now in advanced stages of pharmaceutical development-will soon be available for treatment of a remarkably wide range of serious health conditions with minimal side effects/adverse reactions. Also foreseeable is the advent of a time in which the "one drug-one target" paradigm will be phased out, whereas multitargeted H2S prodrugs find expanding roles in the treatment of highly complex disease states-such paradigm change will prevent polypharmacy and bring about truly disease-modifying outcomes. In the seven articles comprising Parts A and B of this Forum (2-4, 6-9), international experts survey remarkably diverse landscapes of small and large H2S donor molecules, H2S release profiles and mechanisms, pharmacophores/metabolic routes, and potential therapeutic or prophylactic indications. Donors of related sulfur species, such as persufides, SO2, carbon oxysulfide (COS), and carbon disulfide, are examined as well. This Editorial highlights a few of the insights shared by the 32 Forum contributors and includes a proposed classification of H2S/COS prodrugs that is intended to aid in the systematization of this burgeoning field.