AZD9056 / AstraZeneca - LARVOL DELTA

Inhibition of the P2X7 receptor is insufficient to mediate disease in hidradenitis suppurativa, but may restore immune exhaustion: Results of a phase 2 randomized controlled trial of AZD9056 (SID 2025) - "Nonetheless, P2X7 inhibition restored cytokine production in PBMCs, reversing immune exhaustion, possibly via reduced Th1/Th17 expression. While it does not address HS clinical activity, it may enhance immune responses, meriting further investigation for its role in immune dysfunction in HS and other autoimmune diseases."

Clinical • P2 data • Dermatology • Hidradenitis Suppurativa • Immunology • IL13 • IL1B • IL6 • NLRP3 • TNFA

P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research). (PubMed, Int J Surg) - "Our conclusion is that activation of P2X7R promotes the proliferation, metastasis and EMT of GC cells by activating P13/AKT/GSK-3beta signaling, and indicates that P2X7R may become a new potential target for GC treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • CDH1 • CDH2 • GSK3B • MMP2 • MMP9 • VIM • ZEB1

The role of pro-inflammatory and pro-resolving mediators on the development of end-stage liver disease (IARS-SOCCA 2025) - "Macrophages derived from individuals with end-stage liver disease undergoing liver transplantation surgery produce more pro-inflammatory compared to pro-resolving mediators. Interestingly, P2X7R does not play a predominant role in eicosanoid production in Kupffer cells as exhibited by increased production of mediators in the presence of the P2X7R inhibitor, AZD9056. BzATP has known partial affinity for P2X1R and P2Y1R."

Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Role of P2X7 receptor in the progression and clinicopathological characteristics of gastric cancer. (PubMed, Sci Rep) - "While P2X7R antagonists (A438079 and AZD9056) inhibited the proliferation, migration and invasion of gastric cancer cells induced by ATP. Therefore, the data obtained in this experiment suggest that P2X7R may be another potential molecular target for the prevention and treatment of gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor

P2X signaling influences the production of pro-resolving and pro-inflammatory lipid mediators in alveolar macrophages derived from individuals with asthma. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "The early production of the pro-resolving eicosanoids, LXA4 and Resolvin D1, is regulated by P2X, whereas generation of the pro-inflammatory eicosanoid, 15(S)-HETE, is only partially regulated through P2X signaling and reaches maximal production after the peak in pro-resolving eicosanoids."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Purinergic Receptor Activation Stimulates Lipoxin A4 Production in Alveolar Macrophages Derived from Individuals with Asthma (ATS 2022) - "Alveolar macrophages were stimulated with BZ-ATP in the presence or absence of the P2X7-selective antagonist, AZD9056, and the production of Prostaglandin E2 (PGE2), Lipoxin A4 (LXA4), or 15(S)-hydroxyeicosatetraenoic acid (HETE) was quantified using enzyme-linked immunoassays... Both early and late production of LXA4 by alveolar macrophages is regulated by P2X7, whereas generation of 15(S)-HETE and PGE2 is only partially regulated through P2X7 signaling in these cells. Imbalances in eicosanoid production by alveolar macrophages may explain failure of exacerbation resolution in a subset of patients."

Clinical • Asthma • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] P2X7 Receptor Activity Mediates Th17-Specific Self- and Alloreactivity in Non-Human Primates (ATC 2021) - "Importantly, the uncovered inflammatory responses were fully abrogated when performed in the presence of the P2X7R inhibitor, AZD9056... As observed in humans, RM P2X7R activity is involved in uncovered, Th17 specific cellular immune responses. Importantly, by revealing functional polymorphisms consistent with human variations, we validated their rigor as a preclinical model for P2X7R-targeted therapies. Based on these findings, we hypothesize that low pore activity is associated with a tolerogenic state and that P2X7R inhibition could enhance tolerance induction protocols."

Immunology • Inflammation • Transplantation • CD4 • ENTPD1 • IL17A • TGFB1 • VIM

Caspase-11 promotes NLRP3 inflammasome activation via the cleavage of pannexin1 in acute kidney disease. (PubMed, Acta Pharmacol Sin) - "In NRK-52E cells, overexpression of caspase-11 promoted panx1 cleavage; pretreatment with panx1 inhibitor carbenoxolone or knockdown of panx1 significantly attenuated H/R-induced intracellular ATP reduction, extracellular ATP elevation and NLRP3 inflammasome activation without apparent influence on H/R-induced caspase-11 increase; pretreatment with P2X7 receptor inhibitor AZD9056 also attenuated NLRP3 inflammasome activation. The above results demonstrate that the cleavage of panx1 by upregulated caspase-11 is involved in facilitating ATP release and then NLRP3 inflammasome activation in I/R-induced AKI. This study provides new insight into the molecular mechanism of NLRP3 inflammasome activation in AKI."

Journal • Acute Kidney Injury • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • IL1B

PI3K/Akt/GSK-3β signal pathway is involved in P2X7 receptor-induced proliferation and EMT of colorectal cancer cells. (PubMed, Eur J Pharmacol) - "ATP and BzATP increased the expression of P2X7R in CRC cells, while the application of P2X7R antagonist A438079 and AZD9056 decreased the P2X7R expression induced by BzATP. P13/Akt pathway inhibitor LY294002 inhibited the proliferation of CRC cells, and the P13/Akt signaling was required for BzATP induced the proliferation of CRC cells. Our conclusion is that P2X7R mediated the PI3K/Akt/GSK-3beta signaling to promote the proliferation and EMT of CRC, indicating that P2X7R may be used as a potential therapeutic target for CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDH1 • FN1 • GSK3B • TGFB1 • VIM

Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling. (PubMed, Front Cell Dev Biol) - "The results showed that ATP and BzATP significantly increased the inward current and intracellular calcium concentration of LOVO and SW480 cells, while the use of antagonists (A438079 and AZD9056) could reverse the above phenomenon...Our conclusion is that ATP-induced P2 × 7 receptor activation promotes the migration and invasion of colon cancer cells, possibly via the activation of STAT3 pathway. Therefore, the P2 × 7 receptor may be a potential target for the treatment of colon cancer."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CDH1 • MMP2 • VIM • ZEB1

AZD-9056, a P2X7 receptor inhibitor, suppresses ATP-induced melanogenesis. (PubMed, J Dermatol Sci) - No abstract available

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