Hydrogen sulfide-releasing therapeutics - how far have we come in clinical studies?

Abstract

Hydrogen sulfide (H2 S) is the youngest member of the gasotransmitters family consisting of nitric oxide (NO) and carbon monoxide (CO). This signalling molecule is implicated in the regulation of a wide range of processes, such as inflammation, pain, and tissue repair, and has an important role in signalling processes affecting cardiovascular health, either as an independent effector or as an enhancer of the NO system. With the discovery of the H2 S role in the pathogenesis of many diseases, the development of new pharmaceuticals that could be useful in conditions with disturbed levels of endogenous H2 S began. Today, the development of H2 S-releasing drugs has reached the level of clinical studies. Drugs such as SG1002, aimed at the treatment of heart failure, and ATB-346, aimed at the treatment of arthritis, have been tested in Phase I/II clinical studies and have shown significant therapeutic potential. Additionally, it has been shown that some already known drugs, such as zofenopril, produce part of their beneficial effects by releasing H2 S. Evidence from clinical studies presented in this paper encourages further clinical testing of H2 S-based therapeutics and the possibility of their application in a wide range of diseases, such as hypertension, diabetes and chronic kidney disease.

Vodonik-sulfid (H2S) je najmlađi član porodice gasovitih medijatora koju čine azot-oksid (NO) i ugljen-monoksid (CO). Ovaj signalni molekul uključen je u regulaciju širokog spektra procesa, kao što su zapaljenje, bol, reparacija tkiva, i ima važnu ulogu u signalnim procesima koji utiču na zdravlje kardiovaskularnog sistema, bilo kao nezavisni efektor ili kao pojačivač NO signalnog puta. Sa otkrivanjem uloge H 2 S-a u patogenezi mnogih bolesti, započeo je razvoj novih farmaceutika koji bi mogli biti od koristi u stanjima sa poremećenim nivoima endogenog H2 S-a. Razvoj lekova koji oslobađaju H2S danas je dosegao nivo kliničkih studija. Lekovi poput SG1002, za terapiju srčane insuficijencije, i ATB-346, za terapiju artritisa, ispitivani su u Fazi I/II kliničkih studija i pokazali značajan terapijski potencijal. Dodatno, pokazano je da neki već poznati lekovi, poput zofenoprila, deo svojih korisnih efekata ostvaruju upravo oslobađanjem H 2 S-a. Dokazi iz kliničkih studija izneti u ovom radu ohrabruju dalja klinička testiranja terapeutika baziranih na H2 S-u i mogućnost njihove primene u širokom spektru bolesti, poput hipertenzije, dijabetesa i hronične bolesti bubrega.