ArticleThe Journal of biological chemistry2015
Structure Guided Chemical Modifications of Propylthiouracil Reveal Novel Small Molecule Inhibitors of Cytochrome b5 Reductase 3 That Increase Nitric Oxide Bioavailability.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
21 citing papers in PubMed, 34 citations in OpenAlex.
- Cytochrome bBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan.Nature aging · 2025Article
- Identification of metabolism-related subtypes and feature genes in Alzheimer's disease.Journal of translational medicine · 2023Article
- Ordered Motions in the Nitric-Oxide Dioxygenase Mechanism of Flavohemoglobin and Assorted Globins with Tightly Coupled Reductases.Advances in experimental medicine and biology · 2023Article
- Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death.The Journal of clinical investigation · 2022Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Redox Switches Controlling Nitric Oxide Signaling in the Resistance Vasculature and Implications for Blood Pressure Regulation: Mid-Career Award for Research Excellence 2020.Hypertension (Dallas, Tex. : 1979) · 2021Review
- A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19.Scientific reports · 2021Article
- Mapping the SARS-CoV-2-Host Protein-Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics.International journal of molecular sciences · 2021Review
- Data, Reagents, Assays and Merits of Proteomics for SARS-CoV-2 Research and Testing.Molecular & cellular proteomics : MCP · 2020Article
- Loss of smooth muscle CYB5R3 amplifies angiotensin II-induced hypertension by increasing sGC heme oxidation.JCI insight · 2019Article
- Antagonism of Forkhead Box Subclass O Transcription Factors Elicits Loss of Soluble Guanylyl Cyclase Expression.Molecular pharmacology · 2019Article
- Escorting α-globin to eNOS: α-globin-stabilizing protein paves the way.The Journal of clinical investigation · 2018Article
- Cellular and Molecular Mechanisms of Recessive Hereditary Methaemoglobinaemia Type II.Journal of clinical medicine · 2018Review
- Overexpression of CYB5R3 and NQO1, two NADAging cell · 2018Article
- Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.American journal of respiratory cell and molecular biology · 2017Article
- Redox Control of Vascular Function.Arteriosclerosis, thrombosis, and vascular biology · 2017Review
- Regulation of endothelial hemoglobin alpha expression by Kruppel-like factors.Vascular medicine (London, England) · 2017Article
- Cytochrome b5 Reductase 3 Modulates Soluble Guanylate Cyclase Redox State and cGMP Signaling.Circulation research · 2017Article
- Nitric oxide: what's new to NO?American journal of physiology. Cell physiology · 2017Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
NADH cytochrome b5 reductase 3 (CYB5R3) is critical for reductive reactions such as fatty acid elongation, cholesterol biosynthesis, drug metabolism, and methemoglobin reduction. Although the physiological and metabolic importance of CYB5R3 has been established in hepatocytes and erythrocytes, emerging investigations suggest that CYB5R3 is critical for nitric oxide signaling and vascular function. However, advancement toward fully understanding CYB5R3 function has been limited due to a lack of potent small molecule inhibitors. Because of this restriction, we modeled the binding mode of propylthiouracil, a weak inhibitor of CYB5R3 (IC50 = ∼275 μM), and used it as a guide to predict thiouracil-biased inhibitors from the set of commercially available compounds in the ZINC database. Using this approach, we validated two new potent derivatives of propylthiouracil, ZINC05626394 (IC50 = 10.81 μM) and ZINC39395747 (IC50 = 9.14 μM), both of which inhibit CYB5R3 activity in cultured cells. Moreover, we found that ZINC39395747 significantly increased NO bioavailability in renal vascular cells, augmented renal blood flow, and decreased systemic blood pressure in response to vasoconstrictors in spontaneously hypertensive rats. These compounds will serve as a new tool to examine the biological functions of CYB5R3 in physiology and disease and also as a platform for new drug development.
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