ArticleCirculation. Heart failure2021
CRD-733, a Novel PDE9 (Phosphodiesterase 9) Inhibitor, Reverses Pressure Overload-Induced Heart Failure.
Article in Circulation. Heart failure, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial.Journal of the American Heart Association · 2024Trial
- Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- PDE9A Promotes Calcium-Handling Dysfunction in Right Heart Failure via cGMP-PKG Pathway Suppression: A Mechanistic and Therapeutic Review.International journal of molecular sciences · 2025Review
- Phosphodiesterase 9 Inhibition Combined With Valsartan and With Sacubitril/Valsartan in Experimental Ovine Heart Failure.Journal of the American Heart Association · 2024Article
- New and future heart failure drugs.Nature cardiovascular research · 2024Review
- Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.GeroScience · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor.Journal of medicinal chemistry · 2022Article
- Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension: Focus on Phosphodiesterase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology.Cardiovascular research · 2022Review
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling.Frontiers in pharmacology · 2022Article
- Cyclic GMP and PKG Signaling in Heart Failure.Frontiers in pharmacology · 2022Review
- Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice.The Journal of clinical investigation · 2021Article
- Current Modulation of Guanylate Cyclase Pathway Activity-Mechanism and Clinical Implications.Molecules (Basel, Switzerland) · 2021Review
- Mechanisms and Models in Heart Failure: A Translational Approach.Circulation research · 2021Review
- Phosphodiesterase 9 Inhibition in Models of Heart Failure With Preserved Left Ventricular Ejection Fraction: Should We Focus on the Positive or Negative?Circulation. Heart failure · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAugmentation of NP (natriuretic peptide) receptor and cyclic guanosine monophosphate (cGMP) signaling has emerged as a therapeutic strategy in heart failure (HF). cGMP-specific PDE9 (phosphodiesterase 9) inhibition increases cGMP signaling and attenuates stress-induced hypertrophic heart disease in preclinical studies. A novel cGMP-specific PDE9 inhibitor, CRD-733, is currently being advanced in human clinical studies. Here, we explore the effects of chronic PDE9 inhibition with CRD-733 in the mouse transverse aortic constriction pressure overload HF model.
methodsAdult male C57BL/6J mice were subjected to transverse aortic constriction and developed significant left ventricular (LV) hypertrophy after 7 days (
resultsCRD-733 treatment reversed existing LV hypertrophy compared with vehicle (
conclusionsThe PDE9 inhibitor, CRD-733, improves key hallmarks of HF including LV hypertrophy, LV dysfunction, left atrial dilation, and pulmonary edema after pressure overload in the mouse transverse aortic constriction HF model. Additionally, elevated plasma cGMP may be used as a biomarker of target engagement. These findings support future investigation into the therapeutic potential of CRD-733 in human HF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.