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Significance: Shortly after the discovery of the role of hydrogen sulfide (H₂S) in many physiological and pathological processes, attempts were made to develop novel pharmaceuticals that may be of benefit for treatment or prevention of a wide range of disorders. The promise of H₂S-based therapeutics is now being demonstrated in clinical trials.

Recent Advances: H₂S-releasing drugs, such as SG1002 for cardiovascular disorders, and ATB-346 for arthritis, have progressed into clinical trials and have shown considerable promise. Some older drugs, such as zofenopril, have now been recognized to produce at least some of the beneficial effects through release of H₂S.

Critical Issues: There remains a need to better understand the underlying mechanisms for some of the observed effects of H₂S-releasing drugs in a clinical setting, such as the marked increase in analgesic potency that has been observed with ATB …