Identification of novel human CC chemokine receptor 8 (CCR8) antagonists via the synthesis of naphthalene amide and sulfonamide isosteres.

Autor: Verhaegen Y; KU Leuven, Department of Chemistry, Sustainable Chemistry for Metals and Molecules, Celestijnenlaan 200F, box 2404, Leuven 3001 Belgium., Liu L; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, box 1043, Leuven 3000 Belgium., Nguyen TT; KU Leuven, Department of Chemistry, Biochemistry, Molecular and Structural Biology, Celestijnenlaan 200G, box 2403 Leuven 3001 Belgium., Loy TV; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, box 1043, Leuven 3000 Belgium., Schols D; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, box 1043, Leuven 3000 Belgium., Voet ARD; KU Leuven, Department of Chemistry, Biochemistry, Molecular and Structural Biology, Celestijnenlaan 200G, box 2403 Leuven 3001 Belgium., Dehaen W; KU Leuven, Department of Chemistry, Sustainable Chemistry for Metals and Molecules, Celestijnenlaan 200F, box 2404, Leuven 3001 Belgium., De Jonghe S; KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, box 1043, Leuven 3000 Belgium. Electronic address: steven.dejonghe@kuleuven.be.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Apr; Vol. 145, pp. 107181. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1016/j.bioorg.2024.107181
Abstrakt: The human CC chemokine receptor 8 (CCR8) has been extensively pursued as target for the treatment of various inflammatory disorders. More recently, the importance of CCR8 in the tumor microenvironment has been demonstrated, spurring the interest in CCR8 antagonism as therapeutic strategy in immuno-oncology. On a previously described naphthalene sulfonamide with CCR8 antagonistic properties, the concept of isosterism was applied, leading to the discovery of novel CCR8 antagonists with IC 50 values in the nM range in both the CCL1 competition binding and CCR8 calcium mobilization assay. The excellent CCR8 antagonistic activity of the most potent congeners was rationalized by homology molecular modeling.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yenthel Verhaegen reports financial support was provided by Fund for Scientific Research. Libao Liu reports financial support was provided by Guangzhou Elite Project. Steven De Jonghe has patent #Novel CCR8 antagonists pending to KU Leuven. Tom Van Loy has patent #Novel CCR8 antagonists pending to KU Leuven. Dominique Schols has patent #Novel CCR8 antagonists pending to KU Leuven. Wim Dehaen has patent #Novel CCR8 antagonists pending to KU Leuven. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: