ArticleJournal of biomolecular screening2012
Development of a dimethylarginine dimethylaminohydrolase (DDAH) assay for high-throughput chemical screening.
Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors.Biochimica et biophysica acta. General subjects · 2022Pooled it
- Overexpression of alanine-glyoxylate aminotransferase 2 protects from asymmetric dimethylarginine-induced endothelial dysfunction and aortic remodeling.Scientific reports · 2022Article
- Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction.Scientific reports · 2021Article
- Specific Lowering of Asymmetric Dimethylarginine by Pharmacological Dimethylarginine Dimethylaminohydrolase Improves Endothelial Function, Reduces Blood Pressure and Ischemia-Reperfusion Injury.The Journal of pharmacology and experimental therapeutics · 2021Article
- Protein Arginine Methyltransferases in Cardiovascular and Neuronal Function.Molecular neurobiology · 2020Review
- The Second Life of Methylarginines as Cardiovascular Targets.International journal of molecular sciences · 2019Review
- Asymmetric and symmetric dimethylarginines and mortality in patients with hematological malignancies-A prospective study.PloS one · 2018Article
- Human dimethylarginine dimethylaminohydrolase 1 inhibition by proton pump inhibitors and the cardiovascular risk marker asymmetric dimethylarginine: in vitro and in vivo significance.Scientific reports · 2017Article
- Therapeutic Efficacy of Esomeprazole in Cotton Smoke-Induced Lung Injury Model.Frontiers in pharmacology · 2017Article
- How May Proton Pump Inhibitors Impair Cardiovascular Health?American journal of cardiovascular drugs : drugs, devices, and other interventions · 2016Review
- Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development.Molecules (Basel, Switzerland) · 2016Review
- Modulating DDAH/NOS Pathway to Discover Vasoprotective Insulin Sensitizers.Journal of diabetes research · 2016Review
- A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a modulator of cardiovascular nitric oxide.The Journal of pharmacology and experimental therapeutics · 2014Article
- Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine.Circulation · 2013Article
- FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.PloS one · 2013Article
- Discovery of structurally-diverse inhibitor scaffolds by high-throughput screening of a fragment library with dimethylarginine dimethylaminohydrolase.Bioorganic & medicinal chemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Nitric oxide (NO) is a potent signaling molecule that needs to be tightly regulated to maintain metabolic and cardiovascular homeostasis. The nitric oxide synthase (NOS)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is central to this regulation. Specifically, the small-molecule ADMA competitively inhibits NOS, thus lowering NO levels. The majority of ADMA is physiologically metabolized by DDAH, thus maintaining NO levels at a physiological concentration. However, under pathophysiological conditions, DDAH activity is impaired, in part as a result of its sensitivity to oxidative stress. Therefore, the application of high-throughput chemical screening for the discovery of small molecules that could restore or enhance DDAH activity might have significant potential in treating metabolic and vascular diseases characterized by reduced NO levels, including atherosclerosis, hypertension, and insulin resistance. By contrast, excessive generation of NO (primarily driven by inducible NOS) could play a role in idiopathic pulmonary fibrosis, sepsis, migraine headaches, and some types of cancer. In these conditions, small molecules that inhibit DDAH activity might be therapeutically useful. Here, we describe optimization and validation of a highly reproducible and robust assay successfully used in a high-throughput screen for DDAH modulators.
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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.