title: Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28.
abstract: Human cytomegalovirus (HCMV) is a widespread human pathogen, possessing onco-modulatory properties. Constitutive signaling of the HCMV-encoded chemokine receptor US28 and its ability to bind a broad spectrum of chemokines might facilitate HCMV-associated tumor progression. Novel nonpeptidergic chemotypes were identified as neutral antagonists or inverse agonists on US28, that allosterically inhibit chemokine binding to US28.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands. vischer@few.vu.nl
authors.forename: Henry F
authors.initials: HF
authors.lastname: Vischer
authors.forename: Janneke W
authors.initials: JW
authors.lastname: Hulshof
authors.forename: Saskia
authors.initials: S
authors.lastname: Hulscher
authors.forename: Silvina A
authors.initials: SA
authors.lastname: Fratantoni
authors.forename: Mark H P
authors.initials: MH
authors.lastname: Verheij
authors.forename: Jane
authors.initials: J
authors.lastname: Victorina
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Smit
authors.forename: Iwan J P
authors.initials: IJ
authors.lastname: de Esch
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D007192:Indenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D019707:Receptors, Chemokine / Q000819:agonists / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000819:agonists / Q000037:antagonists & inhibitors*
chemical_list: C548617:2-(2,4-dichlorobenzyl)-2,3-dihydro-1H-inden-1-amine; D000588:Amines; D007192:Indenes; D008024:Ligands; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins; D007099:Imipramine