Identification of novel allosteric nonpeptidergic inhibitors of the human cytomegalovirus-encoded chemokine receptor US28 |
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Authors: | Henry F Vischer Janneke W Hulshof Saskia Hulscher Silvina A Fratantoni Mark HP Verheij Jane Victorina Martine J Smit Iwan JP de Esch Rob Leurs |
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Institution: | Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands |
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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. |
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