Recent developments in cGMP research: From mechanisms to medicines and back

Łukowski, Robert; Feil, Robert

doi:10.1111/bph.15824

Cited by 2 publications

(3 citation statements)

References 45 publications

(75 reference statements)

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“…Therefore, cGMP generation via NO-GC and tmGC, cGMP signaling via downstream targets and cGMP degradation have been intensively studied. A variety of excellent manuscripts and review articles summarize all these aspects including a special edition of the British Journal of Pharmacology edited by R. Feil and R. Lukowski in 2021 entitled: “Recent developments in cGMP research: From mechanisms to medicines and back” (Lukowski and Feil 2022 ).…”

Section: Cgmp Signaling Pathwaysmentioning

confidence: 99%

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

Friebe

Kraehling

Russwurm

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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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.

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Section: Cgmp Signaling Pathwaysmentioning

confidence: 99%

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

Friebe

Kraehling

Russwurm

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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“…cGMP levels are necessary to be rapidly adjusted to the basal level since excessive cGMP levels activate cellular signaling cascades that have detrimental effects on the cells. In general, cGMP levels are normalized via two pathways: cGMP degradation by PDEs or cGMP exportation by multidrug resistance-associated proteins (MRPs) [ 38 ]. cGMP is decreased by MRP-dependent cGMP export [ 38 ].…”

Section: Cyclic Guanosine Monophosphate (Cgmp) Signalingmentioning

confidence: 99%

“…In general, cGMP levels are normalized via two pathways: cGMP degradation by PDEs or cGMP exportation by multidrug resistance-associated proteins (MRPs) [ 38 ]. cGMP is decreased by MRP-dependent cGMP export [ 38 ]. MK571, an inhibitor of MRP4 and MRP5, was applied to human coronary artery smooth muscle cells, mouse aorta, and pressure overload-induced HF mouse models.…”

Section: Cyclic Guanosine Monophosphate (Cgmp) Signalingmentioning

confidence: 99%

New Therapeutics for Heart Failure: Focusing on cGMP Signaling

Mangmool

Duangrat

Parichatikanond

et al. 2023

IJMS

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Current drugs for treating heart failure (HF), for example, angiotensin II receptor blockers and β-blockers, possess specific target molecules involved in the regulation of the cardiac circulatory system. However, most clinically approved drugs are effective in the treatment of HF with reduced ejection fraction (HFrEF). Novel drug classes, including angiotensin receptor blocker/neprilysin inhibitor (ARNI), sodium-glucose co-transporter-2 (SGLT2) inhibitor, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, soluble guanylyl cyclase (sGC) stimulator/activator, and cardiac myosin activator, have recently been introduced for HF intervention based on their proposed novel mechanisms. SGLT2 inhibitors have been shown to be effective not only for HFrEF but also for HF with preserved ejection fraction (HFpEF). In the myocardium, excess cyclic adenosine monophosphate (cAMP) stimulation has detrimental effects on HFrEF, whereas cyclic guanosine monophosphate (cGMP) signaling inhibits cAMP-mediated responses. Thus, molecules participating in cGMP signaling are promising targets of novel drugs for HF. In this review, we summarize molecular pathways of cGMP signaling and clinical trials of emerging drug classes targeting cGMP signaling in the treatment of HF.

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Recent developments in cGMP research: From mechanisms to medicines and back

Cited by 2 publications

References 45 publications

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

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

New Therapeutics for Heart Failure: Focusing on cGMP Signaling

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