Nucleotide-Derived Competitive Inhibitors of Ectonucleotidase CD39─A Promising Extracellular Target for Immunotherapy of Cancer
240 nM). Docking into a human CD39 homology model rationalized key interactions. PSB-24379 reduced ATP hydrolysis in melanoma and breast cancer cell membranes and partially reverted ATP-mediated effects on T cell activation and proliferation in an ATP-rich environment. These CD39 inhibitors represent high-quality tool compounds with potential as drugs for immunotherapy of cancer.
Authors
- Constanze C. Schmies
- Laura Schäkel (ORCID: https://orcid.org/0000-0002-8743-8261)
- Salahuddin Mirza (ORCID: https://orcid.org/0000-0002-4944-8282)
- Andreas H. Guse (ORCID: https://orcid.org/0000-0002-3972-401X)
- Riekje Winzer (ORCID: https://orcid.org/0000-0001-9780-5857)
- Katharina Sylvester
- Florian Schwermer (ORCID: https://orcid.org/0000-0002-1881-1982)
- Vittoria Lopez (ORCID: https://orcid.org/0000-0002-6364-7755)
- Ghazl Al Hamwi (ORCID: https://orcid.org/0000-0002-6325-381X)
- Luca Svolacchia Brusoni (ORCID: https://orcid.org/0009-0007-7472-7412)
- Helay Baburi (ORCID: https://orcid.org/0009-0004-5944-3399)
- Chunyang Bi (ORCID: https://orcid.org/0000-0002-3447-6192)
- Patrick Riziki
- Julie Pelletier
- Haneen Al Hroub
- Julia Schilling
- Riham Idris
- Leon Luckenbach
- Luca Raulien
- Areso Ahmadsay
- Jean Sévigny
- Christa E Müller
- Georg Rolshoven
- Eva Tolosa
Institutions
- University of Bonn (DE)
- Universität Hamburg (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Centre d'Immunologie et des Maladies Infectieuses (FR)
- Institute of Immunology (HR)
- Center for Translational Molecular Medicine (NL)
- Centre hospitalier de l'Université Laval (CA)
- Infectiologie et santé publique (FR)
- Instytut Farmaceutyczny (PL)
- Université Laval (CA)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1021/acs.jmedchem.6c00054
- Primary Topic
- Adenosine and Purinergic Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft
- China Postdoctoral Science Foundation
- Government of Jiangsu Province
- Deutsche Krebshilfe
- Natural Sciences and Engineering Research Council of Canada
- Fonds de Recherche du Québec - Santé