title: Renal effects of soluble guanylate cyclase stimulators and activators: a review of the preclinical evidence.
abstract: Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs - sGC stimulators and activators - are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects. Clinical trials are required to confirm these findings in humans, and to ascertain whether these agents could provide a future alternative to guideline-recommended treatments.
authors: Bayer Pharma AG, Wuppertal, Germany; University Halle-Wittenberg, Germany. Electronic address: johannes-peter.stasch@bayer.com.
authors: Johannes-Peter
authors: JP
authors: Stasch
authors: University of Regensburg, Regensburg, Germany.
authors: Jens
authors: J
authors: Schlossmann
authors: University of Potsdam, Potsdam, Germany.
authors: Berthold
authors: B
authors: Hocher
mesh_terms: D000818:Animals; D006162:Guanylate Cyclase / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; C450679:BAY 41-8543; C569640:BAY 60-4552; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat