Academic Journal
Discovery of novel anthraquinone-based P2X7R antagonist that reinvigorates anti-tumor immunity and overcomes PD-1 resistance in breast cancer.
| Τίτλος: | Discovery of novel anthraquinone-based P2X7R antagonist that reinvigorates anti-tumor immunity and overcomes PD-1 resistance in breast cancer. |
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| Συγγραφείς: | Liang C; Henan Provincial Key Laboratory of Pediatric Hematology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018, China; School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, 450001, China., Wang S; College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China., Liu X; College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China., Wang X; College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China., Yuan B; College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China., Wang X; School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, 450001, China., Liu W; Henan Provincial Key Laboratory of Pediatric Hematology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018, China., Wang T; Beijing Children's Hospital, Capital Medical University, Beijing, China., Song C; College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China. Electronic address: chjsong@zzu.edu.cn., Yao Y; School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, 450001, China; Pingyuan Laboratory, Zhengzhou, 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: yongfangyao@zzu.edu.cn., Duan Y; Henan Provincial Key Laboratory of Pediatric Hematology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018, China; The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan, 450053, China. Electronic address: duanyongtao860409@163.com. |
| Πηγή: | European journal of medicinal chemistry [Eur J Med Chem] 2026 Oct 05; Vol. 315, pp. 118924. Date of Electronic Publication: 2026 May 12. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| Ιατρικοί όροι (MeSH): | Breast Neoplasms*/drug therapy , Breast Neoplasms*/pathology , Breast Neoplasms*/immunology , Breast Neoplasms*/metabolism , Receptors, Purinergic P2X7*/metabolism , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/chemical synthesis , Anthraquinones*/pharmacology , Anthraquinones*/chemistry , Anthraquinones*/chemical synthesis , Purinergic P2X Receptor Antagonists*/pharmacology , Purinergic P2X Receptor Antagonists*/chemistry , Purinergic P2X Receptor Antagonists*/chemical synthesis , Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Programmed Cell Death 1 Receptor*/metabolism , Drug Resistance, Neoplasm*/drug effects , Drug Discovery*, Cell Proliferation/drug effects ; Humans ; Animals ; Female ; Mice ; Structure-Activity Relationship ; Drug Screening Assays, Antitumor ; Molecular Structure ; Dose-Response Relationship, Drug |
| Περίληψη: | The P2X7 receptor (P2X7R) is critically involved in tumor progression by promoting cancer cell proliferation, invasion, metastasis, and immune evasion. Through structure-based virtual screening of the TOPSCIENCE L1000 library, we identified pixantrone - an FDA-approved agent - as a promising lead compound targeting P2X7R. Leveraging its well-established safety profile and anthraquinone scaffold, we designed and synthesized a novel series of P2X7R antagonists. Among them, the optimized compound 17d displayed potent antagonistic activity (IC (Copyright © 2026 Elsevier Masson SAS. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Antitumor immunity; Breast cancer; Drug repurposing; P2X7R antagonist; PD-1 resistance |
| Substance Nomenclature: | 0 (Receptors, Purinergic P2X7) 0 (Antineoplastic Agents) 0 (Anthraquinones) 0 (Purinergic P2X Receptor Antagonists) 0 (Programmed Cell Death 1 Receptor) |
| Entry Date(s): | Date Created: 20260517 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.ejmech.2026.118924 |
| PMID: | 42143940 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2026.118924 |