FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2108055984> ?p ?o ?g. }

• W2108055984 endingPage "672" @default.
• W2108055984 startingPage "662" @default.
• W2108055984 abstract "Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulation of xenobiotic metabolism and transporter genes. A recent novel pharmacophore for PXR antagonists was developed using three azoles and consisted of two hydrogen bond acceptor regions and two hydrophobic features. This pharmacophore also suggested an overall small binding site that was identified on the outer surface of the receptor at the AF-2 site and validated by docking studies. Using computational approaches to search libraries of known drugs or commercially available molecules is preferred over random screening. We have now described several new smaller antagonists of PXR discovered with the antagonist pharmacophore with in vitro activity in the low micromolar range [S-p-tolyl 3',5-dimethyl-3,5'-biisoxazole-4'-carbothioate (SPB03255) (IC(50), 6.3 microM) and 4-(3-chlorophenyl)-5-(2,4-dichlorobenzylthio)-4H-1,2,4-triazol-3-ol (SPB00574) (IC(50), 24.8 microM)]. We have also used our computational pharmacophore and docking tools to suggest that most of the known PXR antagonists, such as coumestrol and sulforaphane, could also interact on the outer surface of PXR at the AF-2 domain. The involvement of this domain was also suggested by further site-directed mutagenesis work. We have additionally described an FDA approved prodrug, leflunomide (IC(50), 6.8 microM), that seems to be a PXR antagonist in vitro. These observations are important for predicting whether further molecules may interact with PXR as antagonists in vivo with potential therapeutic applications." @default.
• W2108055984 created "2016-06-24" @default.
• W2108055984 creator A5001163609 @default.
• W2108055984 creator A5001820885 @default.
• W2108055984 creator A5053498507 @default.
• W2108055984 creator A5054253771 @default.
• W2108055984 creator A5061475254 @default.
• W2108055984 creator A5069238430 @default.
• W2108055984 creator A5073973321 @default.
• W2108055984 creator A5079110291 @default.
• W2108055984 creator A5087637065 @default.
• W2108055984 date "2008-06-25" @default.
• W2108055984 modified "2023-09-26" @default.
• W2108055984 title "Computational Discovery of Novel Low Micromolar Human Pregnane X Receptor Antagonists" @default.
• W2108055984 cites W1497750015 @default.
• W2108055984 cites W1534651834 @default.
• W2108055984 cites W1545401674 @default.
• W2108055984 cites W1835084434 @default.
• W2108055984 cites W1965345171 @default.
• W2108055984 cites W1973254690 @default.
• W2108055984 cites W1978889996 @default.
• W2108055984 cites W1980911350 @default.
• W2108055984 cites W1981873124 @default.
• W2108055984 cites W1988564488 @default.
• W2108055984 cites W2003599782 @default.
• W2108055984 cites W2008312146 @default.
• W2108055984 cites W2008525757 @default.
• W2108055984 cites W2008785161 @default.
• W2108055984 cites W2009476878 @default.
• W2108055984 cites W2010124398 @default.
• W2108055984 cites W2015354246 @default.
• W2108055984 cites W2019258148 @default.
• W2108055984 cites W2019349841 @default.
• W2108055984 cites W2029679505 @default.
• W2108055984 cites W2031172040 @default.
• W2108055984 cites W2035000881 @default.
• W2108055984 cites W2041767096 @default.
• W2108055984 cites W2045098692 @default.
• W2108055984 cites W2046157279 @default.
• W2108055984 cites W2049507401 @default.
• W2108055984 cites W2050456292 @default.
• W2108055984 cites W2051746949 @default.
• W2108055984 cites W2054525309 @default.
• W2108055984 cites W2068487566 @default.
• W2108055984 cites W2092190477 @default.
• W2108055984 cites W2098558556 @default.
• W2108055984 cites W2103863911 @default.
• W2108055984 cites W2104114105 @default.
• W2108055984 cites W2109385821 @default.
• W2108055984 cites W2113322724 @default.
• W2108055984 cites W2113504145 @default.
• W2108055984 cites W2114733497 @default.
• W2108055984 cites W2114756989 @default.
• W2108055984 cites W2119325428 @default.
• W2108055984 cites W2120993382 @default.
• W2108055984 cites W2122267374 @default.
• W2108055984 cites W2127226545 @default.
• W2108055984 cites W2128999057 @default.
• W2108055984 cites W2129965508 @default.
• W2108055984 cites W2131792166 @default.
• W2108055984 cites W2140975778 @default.
• W2108055984 cites W2148248538 @default.
• W2108055984 cites W2154120770 @default.
• W2108055984 cites W2157906581 @default.
• W2108055984 cites W2228301361 @default.
• W2108055984 cites W2949504121 @default.
• W2108055984 doi "https://doi.org/10.1124/mol.108.049437" @default.
• W2108055984 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18579710" @default.
• W2108055984 hasPublicationYear "2008" @default.
• W2108055984 type Work @default.
• W2108055984 sameAs 2108055984 @default.
• W2108055984 citedByCount "68" @default.
• W2108055984 countsByYear W21080559842012 @default.
• W2108055984 countsByYear W21080559842013 @default.
• W2108055984 countsByYear W21080559842014 @default.
• W2108055984 countsByYear W21080559842015 @default.
• W2108055984 countsByYear W21080559842016 @default.
• W2108055984 countsByYear W21080559842017 @default.
• W2108055984 countsByYear W21080559842018 @default.
• W2108055984 countsByYear W21080559842019 @default.
• W2108055984 countsByYear W21080559842020 @default.
• W2108055984 countsByYear W21080559842021 @default.
• W2108055984 countsByYear W21080559842022 @default.
• W2108055984 crossrefType "journal-article" @default.
• W2108055984 hasAuthorship W2108055984A5001163609 @default.
• W2108055984 hasAuthorship W2108055984A5001820885 @default.
• W2108055984 hasAuthorship W2108055984A5053498507 @default.
• W2108055984 hasAuthorship W2108055984A5054253771 @default.
• W2108055984 hasAuthorship W2108055984A5061475254 @default.
• W2108055984 hasAuthorship W2108055984A5069238430 @default.
• W2108055984 hasAuthorship W2108055984A5073973321 @default.
• W2108055984 hasAuthorship W2108055984A5079110291 @default.
• W2108055984 hasAuthorship W2108055984A5087637065 @default.
• W2108055984 hasConcept C104317684 @default.
• W2108055984 hasConcept C107824862 @default.
• W2108055984 hasConcept C108215921 @default.
• W2108055984 hasConcept C132040763 @default.
• W2108055984 hasConcept C159110408 @default.

• next