ArticleScientific reports2016
Harnessing the natural inhibitory domain to control TNFα Converting Enzyme (TACE) activity in vivo.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
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- Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.Molecular cell · 2024Article
- ADME profiling, molecular docking, DFT, and MEP analysis reveal cissamaline, cissamanine, and cissamdine fromRSC advances · 2024Article
- Redefining metalloproteases specificity through network proteolysis.Trends in molecular medicine · 2024Review
- Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Breast Cancer Macrophage Heterogeneity and Self-renewal are Determined by Spatial Localization.bioRxiv : the preprint server for biology · 2023Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- Intestinal Damage, Inflammation and Microbiota Alteration during COVID-19 Infection.Biomedicines · 2023Review
- Blockade of the protease ADAM17 ameliorates experimental pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?Cancers · 2022Review
- Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.The Journal of experimental medicine · 2022Article
- Management of inflammatory bowel disease in the COVID-19 era.Intestinal research · 2022Review
- The dichotomous outcomes of TNFα signaling in CD4Frontiers in immunology · 2022Review
- Metabolic Messengers: tumour necrosis factor.Nature metabolism · 2021Review
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- Impact of the COVID-19 pandemic on inflammatory bowel disease patients: A review of the current evidence.World journal of gastroenterology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated activity of A Disintegrin And Metalloproteinase 17 (ADAM17)/TNFα Converting Enzyme (TACE) is associated with inflammatory disorders and cancer progression by releasing regulatory membrane-tethered proteins like TNFα, IL6R and EGFR ligands. Although specific inhibition of TACE is thought to be a viable strategy for inflammatory disorders and for malignancies treatment, the generation of effective inhibitors in vivo has been proven to be challenging. Here we report on the development of a protein inhibitor that leverages the endogenous modulator of TACE. We have generated a stable form of the auto-inhibitory TACE prodomain (TPD), which specifically inhibits in vitro and cell-surface TACE, but not the related ADAM10, and effectively modulated TNFα secretion in cells. TPD significantly attenuated TACE-mediated disease models of sepsis, rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and reduced TNFα in synovial fluids from RA patients. Our results demonstrate that intervening with endogenous ADAM sheddase modulatory mechanisms holds potential as a general strategy for the design of ADAM inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.