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KMID : 0370220170610060317
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Yakhak Hoeji
2017 Volume.61 No. 6 p.317 ~ p.325
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Pharmacological Regulation of the H2S and Inhibitors
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Min Young-Sil
Sohn Uy-Dong
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Abstract
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Hydrogen sulfide (H2S) is an endogenous gaseous molecule that regulates physiologic and pathophysiological processes in various cells and tissues. H2S levels are decreased in diabetes mellitus, ischemia, and aging, and increased in inflammation and cancer. Various donors with diverse H2S release profiles include oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and mitochondrial-targeted compounds. Clinically approved nonsteroidal anti-inflammatory drugs are also coupled with H2S-donating groups; ATB-346, an H2S-donating derivative of naproxen, is one such compound in clinical trials. Pharmacological inhibitors of H2S synthesis include small molecule compounds targeting each of the three H2S-producing enzymes?cystathionine-β-synthase (CBS), cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Cell-permeable prodrugs of the CBS inhibitors, aminooxyacetate or benserazide, may serve as starting points for future clinical development. In this paper, we review H2S donors and H2S biosynthesis inhibitors in light of their modes of action, biological effects, and potential therapeutic utility.
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KEYWORD
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Hydrogen sulfide, Donors, Inhibitors
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