ArticleInternational journal of molecular sciences2021
TAS-116, a Well-Tolerated Hsp90 Inhibitor, Prevents the Activation of the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- Hsp90 inhibition attenuates the 1, 2-Dichloroethane-induced cognitive impairment by blocking NLRP3 inflammasome activation in mice.Toxicology research · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- HSP90, a Common Therapeutic Target for Suppressing Skin Injury Caused by Exposure to Chemically Diverse Classes of Blistering Agents.The Journal of pharmacology and experimental therapeutics · 2024Article
- Drugs in the GIST Field (Therapeutic Targets and Clinical Trial Staging).Current drug delivery · 2024Article
- Potential plasma biomarkers at low altitude for prediction of acute mountain sickness.Frontiers in immunology · 2023Article
- The NLRP3-Inflammasome in Health and Disease.International journal of molecular sciences · 2022Article
- Epoxomicin, a Selective Proteasome Inhibitor, Activates AIM2 Inflammasome in Human Retinal Pigment Epithelium Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Optimizing antidotal treatment with the oral HSP90 inhibitor TAS-116 against hydrochloric acid-induced pulmonary fibrosis in mice.Frontiers in pharmacology · 2022Article
- Pyroptosis: A New Insight Into Eye Disease Therapy.Frontiers in pharmacology · 2021Review
- The inflammasome pathway: A key player in ocular surface and anterior segment diseases.Survey of ophthalmologyReview
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1β. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NLRP3 activation in human retinal pigment epithelial (RPE) cells; these are cells which play a central role in the pathogenesis of AMD. In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects, including ocular toxicity. Here, we have tested the effects of a novel Hsp90 inhibitor, TAS-116, on NLRP3 activation using geldanamycin as a reference compound. Using our existing protocol, inflammasome activation was induced in IL-1α-primed ARPE-19 cells with the proteasome and autophagy inhibitors MG-132 and bafilomycin A1, respectively. Intracellular caspase-1 activity was determined using a commercial caspase-1 activity kit and the FLICA assay. The levels of IL-1β were measured from cell culture medium samples by ELISA. Cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) measurements. Our findings show that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1β. TAS-116 has a better
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