1297549-05-3Relevant articles and documents
Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)
Hahn, Michael G.,Lampe, Thomas,El Sheikh, Sherif,Griebenow, Nils,Woltering, Elisabeth,Schlemmer, Karl-Heinz,Dietz, Lisa,Gerisch, Michael,Wunder, Frank,Becker-Pelster, Eva-Maria,Mondritzki, Thomas,Tinel, Hanna,Knorr, Andreas,Kern, Armin,Lang, Dieter,Hueser, Joerg,Schomber, Tibor,Benardeau, Agnes,Eitner, Frank,Truebel, Hubert,Mittendorf, Joachim,Kumar, Vijay,Van Den Akker, Focco,Schaefer, Martina,Geiss, Volker,Sandner, Peter,Stasch, Johannes-Peter
supporting information, p. 5323 - 5344 (2021/05/06)
Herein we describe the discovery, mode of action, and preclinical characterization of the soluble guanylate cyclase (sGC) activator runcaciguat. The sGC enzyme, via the formation of cyclic guanosine monophoshphate, is a key regulator of body and tissue homeostasis. sGC activators with their unique mode of action are activating the oxidized and heme-free and therefore NO-unresponsive form of sGC, which is formed under oxidative stress. The first generation of sGC activators like cinaciguat or ataciguat exhibited limitations and were discontinued. We overcame limitations of first-generation sGC activators and identified a new chemical class via high-throughput screening. The investigation of the structure-activity relationship allowed to improve potency and multiple solubility, permeability, metabolism, and drug-drug interactions parameters. This program resulted in the discovery of the oral sGC activator runcaciguat (compound 45, BAY 1101042). Runcaciguat is currently investigated in clinical phase 2 studies for the treatment of patients with chronic kidney disease and nonproliferative diabetic retinopathy.
