{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:34:55Z","timestamp":1760142895765,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSU Health Profession\u2019s Division Chancellor\u2019s Award","award":["HPD"],"award-info":[{"award-number":["HPD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Rheumatoid arthritis is a systemic autoimmune inflammatory disease that affects millions of people worldwide. There are multiple disease-modifying anti-rheumatic drugs available; however, many patients do not respond to any treatment. A disintegrin and metalloproteinase 10 has been suggested as a potential new target for RA due to its role in the release of multiple pro- and anti-inflammatory factors from cell surfaces. In the present study, we determined the pharmacokinetic parameters and in vivo efficacy of a compound CID3117694 from a novel class of non-zinc-binding inhibitors. Oral bioavailability was demonstrated in the blood and synovial fluid after a 10 mg\/kg dose. To test efficacy, we established the collagen-induced arthritis model in mice. CID3117694 was administered orally at 10, 30, and 50 mg\/kg\/day for 28 days. CID3117694 was able to dose-dependently improve the disease score, decrease RA markers in the blood, and decrease signs of inflammation, hyperplasia, pannus formation, and cartilage erosion in the affected joints compared to the untreated control. Additionally, mice treated with CID 3117694 did not exhibit any clinical signs of distress, suggesting low toxicity. The results of this study suggest that the inhibition of ADAM10 exosite can be a viable therapeutic approach to RA.<\/jats:p>","DOI":"10.3390\/ph17010087","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T10:48:06Z","timestamp":1704797286000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An ADAM10 Exosite Inhibitor Is Efficacious in an In Vivo Collagen-Induced Arthritis Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Juan","family":"Diez","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7152-4739","authenticated-orcid":false,"given":"Michael E.","family":"Selsted","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90089, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas D.","family":"Bannister","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 120 Scripps Way, Jupiter, FL 33458, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy","family":"Minond","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"},{"name":"Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3301 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","unstructured":"American College of Rheumatology (2023, September 25). 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