Soluble GC stimulators and activators: Past, present and future.

Autor: Sandner P; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany.; Institute of Pharmacology, Hannover Medical School, Hanover, Germany., Follmann M; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany., Becker-Pelster E; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany., Hahn MG; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany., Meier C; Pharmaceuticals Medical Affairs and Pharmacovigilance, Bayer AG, Berlin, Germany., Freitas C; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany., Roessig L; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany., Stasch JP; Pharmaceuticals Research & Development, Bayer AG, Wuppertal, Germany.; Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2024 Nov; Vol. 181 (21), pp. 4130-4151. Date of Electronic Publication: 2021 Dec 01.
DOI: 10.1111/bph.15698
Abstrakt: The discovery of soluble GC (sGC) stimulators and sGC activators provided valuable tools to elucidate NO-sGC signalling and opened novel pharmacological opportunities for cardiovascular indications and beyond. The first-in-class sGC stimulator riociguat was approved for pulmonary hypertension in 2013 and vericiguat very recently for heart failure. sGC stimulators enhance sGC activity independent of NO and also act synergistically with endogenous NO. The sGC activators specifically bind to, and activate, the oxidised haem-free form of sGC. Substantial research efforts improved on the first-generation sGC activators such as cinaciguat, culminating in the discovery of runcaciguat, currently in clinical Phase II trials for chronic kidney disease and diabetic retinopathy. Here, we highlight the discovery and development of sGC stimulators and sGC activators, their unique modes of action, their preclinical characteristics and the clinical studies. In the future, we expect to see more sGC agonists in new indications, reflecting their unique therapeutic potential.
(© 2021 Bayer AG. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
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