ArticleInflammation2026
Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.
Article in Inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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16 authors.
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Abstract
Purinergic receptor (P2X7R), an adenosine triphosphate (ATP) gated nonselective cation channel, is an emerging target for several neurodegenerative conditions, including retinal degeneration. In particular, P2X7R has an established role in multiple inflammatory and immune responses, being implicated in the formation and activation of NLRP3 inflammasome leading to inflammatory priming and release of immune cytokines. Despite several efforts in P2X7R antagonist design, no drugs have reached the market yet. In this perspective, through an integrated in silico and in vitro approach, we aimed to repurpose FDA approved drugs in search of novel safe treatments for retinal degenerative diseases, where P2X7R has been found to play a detrimental role. Virtual screening of about 10,000 FDA approved drugs identified 6 putative P2X7 antagonists. Three out of these six compounds inhibited hP2X7, but not rat receptors, while only one compound, tipranavir, inhibited also mouse P2X7R. Then, for these three P2X7R antagonists, namely bazedoxifene, teniposide and tipranavir, we have evaluated the in vitro tolerability by treating immortalized human Müller cells (MIO-M1), primary retinal endothelial cells (HRECs), human umbilical vein endothelial cells (HUVECs) and human retinal pigmented epithelial cells (hRPEs). Tipranavir and teniposide were well tolerated by the mentioned retinal cells, thereby they have been further evaluated in in vitro models of glaucoma, diabetic retinopathy, and age-related macular degeneration. Tipranavir and teniposide showed retinal cell protection, modulating the expression of HIF-1α, VEGF-A, and inflammatory cytokines. Therefore, these compounds are worthy of further investigation to manage retinal degenerative conditions.
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