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The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y inhibitor, platelets from healthy volunteers receiving aspirin or P2Y inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.
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http://dx.doi.org/10.1016/j.jacbts.2024.05.014 | DOI Listing |
Drug Des Devel Ther
August 2025
Henan Provincial Key Laboratory of Pediatric Hematology, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Purpose: The P2Y receptor (P2YR) is closely associated with several inflammatory diseases in humans. Although several P2YR antagonists have been reported to date, few have been successfully developed as therapeutic drugs, and none have entered clinical trials. We aimed to obtain P2YR antagonists with high antagonistic activity and druggability for further investigation into anti-inflammatory drugs.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Center for Non-coding RNA Medicine, Peking University Health Science Center, Beijing, 100191, China.
Although hepatocyte-released adenosine triphosphate (ATP) plays important roles in maintaining metabolic homeostasis, how its hydrolyzation outside hepatocytes impacts on glucolipid metabolism remains unclear. The authors aim to identify the enzyme(s) that hydrolyzes hepatocyte-secreted ATP to regulate metabolic homeostasis. All known ATP-hydrolyzing enzymes are expressed with the highest expression of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) in hepatocytes.
View Article and Find Full Text PDFDrug Discov Today
September 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China; Pingyuan Laboratory, Zhengzhou 450001, China. Electronic address:
P2YR, a target that has garnered extensive research attention in recent years, has been implicated in a diverse range of diseases. Specifically, abnormally high expression levels of P2YR have been identified in various tumor tissues and cells and are closely associated with the degree of malignancy and metastasis of the tumor. Antagonists against P2YR have been shown to effectively block signaling pathways that promote tumor growth, thereby inhibiting cancer cell proliferation, migration, and invasion.
View Article and Find Full Text PDFExpert Rev Cardiovasc Ther
September 2025
Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Caserta, Italy.
Introduction: Cangrelor is the only parenteral P2Y receptor antagonist currently recommended for the prevention of periprocedural thrombotic complications in P2Y inhibitor-naïve patients undergoing percutaneous coronary intervention (PCI).
Areas Covered: This review provides a comprehensive analysis of the pharmacological properties and administration strategies of cangrelor in PCI, summarizes the latest evidence from clinical trials and real-world studies, and discusses potential future directions for its application in clinical practice. Literature search was conducted using PubMed up to May 2025.
J Med Chem
August 2025
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China.
The P2Y receptor is a promising target for treating an ischemic stroke. Herein, a conformational restriction strategy was applied to improve the brain exposure of our previously reported P2Y antagonist HNW001. Compound , containing an imidazo[1,5-]pyrazine scaffold, turned out to be a remarkable P2Y antagonist (IC = 1.
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