Related Experiment Video
Updated: Nov 8, 2025

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Discovery of the Soluble Guanylate Cyclase Activator Runcaciguat (BAY 1101042)
Michael G Hahn1, Thomas Lampe1, Sherif El Sheikh1
1Research and Development, Bayer AG, Pharmaceuticals, Aprather Weg 18a, 42113 Wuppertal, Germany.
Abstract:
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.
More Related Videos
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
09:39Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Related Concept Videos
Rab Cascades
GPCRs Regulate Adenylyl Cylase Activity
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...