A set of experimentally validated decoys for the human CC chemokine receptor 7 (CCR7) obtained by virtual screening

Proj, Matic (author), De Jonghe, Steven (author), Van Loy, Tom (author), Jukič, Marko (author), Meden, Anže (author), Ciber, Luka (author), Podlipnik, Črtomir (author), Grošelj, Uroš (author), Konc, Janez (author), Schols, Dominique (author), Gobec, Stanislav (author)

We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the in silico hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys.

• Language: English
• Keywords: virtual screening, decoys, chemical library, computer-aided drug design, CCR7, GPCR
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 13 str.
• Numbering: Vol. 13, art. 855653
• PID: 20.500.12556/RUL-145326
• UDC: 61+615
• ISSN on article: 1663-9812
• DOI: 10.3389/fphar.2022.855653
• COBISS.SI-ID: 101491459
• Publication date in RUL: 17.04.2023

Record is a part of a journal

• Title: Frontiers in pharmacology
• Shortened title: Front Pharmacol
• Publisher: Frontiers Media
• ISSN: 1663-9812
• COBISS.SI-ID: 29551833

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: virtualno rešetanje, vabe, kemična knjižnica, računalniško podprto načrtovanje zdravil, kemokinski receptor, citokini

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: Other - Other funder or multiple funders
• Funding programme: CELSA