| http://purl.uniprot.org/citations/24342772 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24342772 | http://www.w3.org/2000/01/rdf-schema#comment | "The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N,N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR)7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti-double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.113.089821"xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Liu C."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Liu D."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Shen Y."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Yang H."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Zheng W."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Zhao Y."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Yu M."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Rose J."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Latz E."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Hansen H."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Chow J."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Shaffer C."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Genest M."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Gusovsky F."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Mempel T.R."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Ishizaka S.T."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Lamphier M."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Spyvee M."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Rowbottom C."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/author | "Twine N.C."xsd:string |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24342772 | http://purl.uniprot.org/core/name | "Mol Pharmacol"xsd:string |