The 10th International Conference on cGMP 2022: recent trends in cGMP research and development-meeting report

Abstract

Increasing cGMP is a unique therapeutic principle, and drugs inhibiting cGMP-degrading enzymes or stimulating cGMP production are approved for the treatment of various diseases such as erectile dysfunction, coronary artery disease, pulmonary hypertension, chronic heart failure, irritable bowel syndrome, or achondroplasia. In addition, cGMP-increasing therapies are preclinically profiled or in clinical development for quite a broad set of additional indications, e.g., neurodegenerative diseases or different forms of dementias, bone formation disorders, underlining the pivotal role of cGMP signaling pathways. The fundamental understanding of the signaling mediated by nitric oxide-sensitive (soluble) guanylyl cyclase and membrane-associated receptor (particulate) guanylyl cyclase at the molecular and cellular levels, as well as in vivo, especially in disease models, is a key prerequisite to fully exploit treatment opportunities and potential risks that could be associated with an excessive increase in cGMP. Furthermore, human genetic data and the clinical effects of cGMP-increasing drugs allow back-translation into basic research to further learn about signaling and treatment opportunities. The biannual international cGMP conference, launched nearly 20 years ago, brings all these aspects together as an established and important forum for all topics from basic science to clinical research and pivotal clinical trials. This review summarizes the contributions to the "10th cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications," which was held in Augsburg in 2022 but will also provide an overview of recent key achievements and activities in the field of cGMP research.

Keywords: Guanylyl cyclases; Mosliciguat; NO-GC; Natriuretic peptides; Nitric oxide; Phosphodiesterases; Praliciguat; Riociguat; Runcaciguat; Vericiguat; cGMP; sGC activators; sGC stimulators.

Fig. 1

History of the International Conference on cGMP: Generators, Effectors and Therapeutic Implications. The meeting series started in Leipzig in 2003, followed by Potsdam (2005), Dresden (2007), Regensburg (2009), Halle (Saale) (2011), Erfurt (2013), Trier (2015), Bamberg (2017), and Mainz (2019). The meeting is held every second year, but the 2021 meeting had to be postponed due to the COVID19 pandemic and was now held in 2022 in Augsburg

Fig. 2

Participants of the 10th International Conference on cGMP, held in Augsburg, Germany, from June 17–19, 2022. For program and meeting information see https://www.cyclicgmp.net/index.html; For abstracts, please reach out to J Transl Med 2022 (online publication estimated for Dec 2022)

Fig. 3

Abbreviations: cAMP, cyclic adenosine monophosphate; cGK, cGMP-dependent protein kinase; cGMP, cyclic guanosine monophosphate; GC, guanylyl cyclase; GC-A, guanylyl cyclase A; GC-B, guanylyl cyclase B; GMP, guanosine monophosphate; GTN, glyceryl trinitrate; 5′-GTP, guanosine triphosphate; NO, nitric oxide; NO-GC, NO-sensitive (soluble) guanylyl cyclase (also sGC); NP, natriuretic peptide(s); PDE, phosphodiesterase (adapted from Lukowski and Feil, BJP 2022; created with BioRender.com)

Fig. 4

Structures of sGC-agonist compounds which are currently marketed (Riociguat and Vericiguat) or in clinical development (created with BIOVIA Draw)