Matches in SemOpenAlex for { <https://semopenalex.org/work/W273230620> ?p ?o ?g. }
- W273230620 endingPage "16872" @default.
- W273230620 startingPage "16861" @default.
- W273230620 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." @default.
- W273230620 created "2016-06-24" @default.
- W273230620 creator A5005780035 @default.
- W273230620 creator A5019947935 @default.
- W273230620 creator A5023869904 @default.
- W273230620 creator A5029845193 @default.
- W273230620 creator A5033317704 @default.
- W273230620 creator A5040674543 @default.
- W273230620 creator A5040700924 @default.
- W273230620 creator A5057662208 @default.
- W273230620 creator A5059885979 @default.
- W273230620 creator A5070796633 @default.
- W273230620 creator A5079581156 @default.
- W273230620 creator A5082132567 @default.
- W273230620 creator A5087456017 @default.
- W273230620 date "2015-07-01" @default.
- W273230620 modified "2023-10-15" @default.
- W273230620 title "Structure Guided Chemical Modifications of Propylthiouracil Reveal Novel Small Molecule Inhibitors of Cytochrome b5 Reductase 3 That Increase Nitric Oxide Bioavailability" @default.
- W273230620 cites W1488907063 @default.
- W273230620 cites W1505834253 @default.
- W273230620 cites W1970677658 @default.
- W273230620 cites W1975110930 @default.
- W273230620 cites W1976520934 @default.
- W273230620 cites W1985925852 @default.
- W273230620 cites W1997023449 @default.
- W273230620 cites W2003169571 @default.
- W273230620 cites W2007737411 @default.
- W273230620 cites W2009447874 @default.
- W273230620 cites W2024227232 @default.
- W273230620 cites W2027482274 @default.
- W273230620 cites W2028629022 @default.
- W273230620 cites W2059360988 @default.
- W273230620 cites W2059628610 @default.
- W273230620 cites W2064023459 @default.
- W273230620 cites W2064562921 @default.
- W273230620 cites W2068477954 @default.
- W273230620 cites W2073800697 @default.
- W273230620 cites W2092145002 @default.
- W273230620 cites W2099001405 @default.
- W273230620 cites W2104104493 @default.
- W273230620 cites W2105890957 @default.
- W273230620 cites W2123631512 @default.
- W273230620 cites W2150302448 @default.
- W273230620 cites W2154811651 @default.
- W273230620 cites W2158294086 @default.
- W273230620 cites W2167974197 @default.
- W273230620 cites W2169182236 @default.
- W273230620 cites W2322828254 @default.
- W273230620 cites W2409770896 @default.
- W273230620 cites W40268261 @default.
- W273230620 doi "https://doi.org/10.1074/jbc.m114.629964" @default.
- W273230620 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4505432" @default.
- W273230620 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26001785" @default.
- W273230620 hasPublicationYear "2015" @default.
- W273230620 type Work @default.
- W273230620 sameAs 273230620 @default.
- W273230620 citedByCount "28" @default.
- W273230620 countsByYear W2732306202016 @default.
- W273230620 countsByYear W2732306202017 @default.
- W273230620 countsByYear W2732306202018 @default.
- W273230620 countsByYear W2732306202019 @default.
- W273230620 countsByYear W2732306202020 @default.
- W273230620 countsByYear W2732306202021 @default.
- W273230620 countsByYear W2732306202022 @default.
- W273230620 countsByYear W2732306202023 @default.
- W273230620 crossrefType "journal-article" @default.
- W273230620 hasAuthorship W273230620A5005780035 @default.
- W273230620 hasAuthorship W273230620A5019947935 @default.
- W273230620 hasAuthorship W273230620A5023869904 @default.
- W273230620 hasAuthorship W273230620A5029845193 @default.
- W273230620 hasAuthorship W273230620A5033317704 @default.
- W273230620 hasAuthorship W273230620A5040674543 @default.
- W273230620 hasAuthorship W273230620A5040700924 @default.
- W273230620 hasAuthorship W273230620A5057662208 @default.
- W273230620 hasAuthorship W273230620A5059885979 @default.
- W273230620 hasAuthorship W273230620A5070796633 @default.
- W273230620 hasAuthorship W273230620A5079581156 @default.
- W273230620 hasAuthorship W273230620A5082132567 @default.
- W273230620 hasAuthorship W273230620A5087456017 @default.
- W273230620 hasBestOaLocation W2732306201 @default.
- W273230620 hasConcept C134651460 @default.
- W273230620 hasConcept C178790620 @default.
- W273230620 hasConcept C181199279 @default.
- W273230620 hasConcept C181389837 @default.
- W273230620 hasConcept C185592680 @default.
- W273230620 hasConcept C2775960720 @default.
- W273230620 hasConcept C2779384962 @default.
- W273230620 hasConcept C519581460 @default.
- W273230620 hasConcept C55493867 @default.
- W273230620 hasConcept C71315377 @default.
- W273230620 hasConcept C71924100 @default.
- W273230620 hasConcept C98274493 @default.
- W273230620 hasConceptScore W273230620C134651460 @default.
- W273230620 hasConceptScore W273230620C178790620 @default.
- W273230620 hasConceptScore W273230620C181199279 @default.
- W273230620 hasConceptScore W273230620C181389837 @default.
- W273230620 hasConceptScore W273230620C185592680 @default.
- W273230620 hasConceptScore W273230620C2775960720 @default.