{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:58:24Z","timestamp":1790686704877,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2003,9,11]],"date-time":"2003-09-11T00:00:00Z","timestamp":1063238400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The transcription of several cytokines, cell adhesion molecules, and enzymes involved in the inflammatory and destructive mechanisms of rheumatoid arthritis is dependent on nuclear factor \u03baB (NF\u2010\u03baB). Because I\u03baB kinase (IKK) is critical in transducing the signal\u2010inducible activation of NF\u2010\u03baB, we examined whether the highly selective and orally bioavailable IKK inhibitor BMS\u2010345541 is efficacious against collagen\u2010induced arthritis (CIA) in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Arthritis in DBA\/1LacJ male mice was induced by subcutaneous immunization with bovine type II collagen on day 0 and day 21. BMS\u2010345541 was administered perorally daily, either prophylactically (before disease onset) or therapeutically (after disease onset). Clinical assessment of the incidence and severity of disease was conducted throughout the study, and histologic evaluation was performed at the time of study termination (day 42).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When administered prophylactically, BMS\u2010345541 (in a dose range of 10\u2013100 mg\/kg) was effective, in a dose\u2010dependent manner, in reducing the incidence of disease and inhibiting clinical signs of disease. Histologic evaluation of the joints showed that both inflammation and joint destruction were blocked by the IKK inhibitor. Message levels of interleukin\u20101\u03b2 in the joints were also dose\u2010dependently inhibited in the mice that received BMS\u2010345541. Dose\u2010dependent efficacy in terms of both disease severity and histologic end points was observed with the therapeutic dosing regimen of BMS\u2010345541, with use of the 100\u2010mg\/kg dose resulting in resolution of disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IKK plays a key role in CIA in mice, and inhibitors of this enzyme represent a promising target for the development of novel agents to treat rheumatoid arthritis and other inflammatory diseases. BMS\u2010345541 represents the first example of an inhibitor of IKK that has antiinflammatory activity in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.11131","type":"journal-article","created":{"date-parts":[[2003,9,16]],"date-time":"2003-09-16T14:43:17Z","timestamp":1063723397000},"page":"2652-2659","source":"Crossref","is-referenced-by-count":194,"title":["A highly selective inhibitor of I\u03baB kinase, BMS\u2010345541, blocks both joint inflammation and destruction in collagen\u2010induced arthritis in mice"],"prefix":"10.1002","volume":"48","author":[{"given":"Kim W.","family":"McIntyre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Shuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Gillooly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Dambach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Pattoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia\u2010Di","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Christopher","family":"Zusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,9,11]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.10.110194.002201"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81318-5"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5668"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/scbi.1997.0058"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878466"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.11884"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.1.376"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7844"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.15.9942"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.6.1413"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2705"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00599-2"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209677200"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/019262339902700125"},{"key":"e_1_2_5_17_2","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.4049\/jimmunol.163.9.5049","article-title":"IL\u20101\u03b1\u03b2 blockade prevents cartilage and bone destruction in murine type II collagen\u2010induced arthritis, whereas TNF\u2010\u03b1 blockade only ameliorates joint inflammation","volume":"163","author":"Joosten LAB","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01267.x"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200108)44:8<1897::AID-ART328>3.0.CO;2-4"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.11.6602"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar398"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0940557"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5412.321"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/75057"},{"key":"e_1_2_5_25_2","first-page":"1149","article-title":"Delivery of I\u03baB superrepressor gene with adenovirus reduces early alcohol\u2010induced liver injury in rats","volume":"6","author":"Uesugi T","year":"2000","journal-title":"Hepatology"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.11131","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.11131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T19:54:11Z","timestamp":1698782051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.11131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":24,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1002\/art.11131"],"URL":"https:\/\/doi.org\/10.1002\/art.11131","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]}}}