{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:17:13Z","timestamp":1771003033692,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,4,12]],"date-time":"2004-04-12T00:00:00Z","timestamp":1081728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,8,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CHS 828, a pyridyl cyanoguanidine, has been shown to exert a significant antitumor effect in preclinical tests <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and CHS 828 is in phase I\/II clinical trials. We have investigated the effect of CHS 828 on the nuclear factor\u2010\u03baB (NF\u2010\u03baB) because of its well\u2010known role in the control of cell division and apoptosis. CHS 828 is able to inhibit the lipopolysaccharide (LPS)\u2010induced nuclear localization as well as the transcriptional activity of NF\u2010\u03baB in human THP\u20101 leukemia cells. Moreover, CHS 828 has also been shown to inhibit the LPS\u2010induced degradation of the I\u03baB\u03b1 and I\u03baB\u03b2 in THP\u20101 cells, leading us to identify the I\u03baB kinase complex as a molecular target of CHS 828. The IKK activity is inhibited by CHS 828 with an IC<jats:sub>50<\/jats:sub> of 8 nM. The inhibition of the IKK activity by different CHS 828 analogues correlates well with the inhibition of NYH small cell lung cancer cell proliferation <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Moreover, the inhibition of NF\u2010\u03baB transcriptional activity in different cancer cell lines by CHS 828 correlates to some extent with the reduction by CHS 828 of the size of the corresponding xenografts. Activation of NF\u2010\u03baB has been shown to induce expression of antiapoptotic proteins, and cancer cells have been shown to have high levels of constitutively active NF\u2010\u03baB. Therefore, we hypothesize that the anticancer activity of CHS 828 is due to inhibition of the IKK activity by which the antiapoptotic protection of NF\u2010\u03baB is removed, leading to the promotion of apoptosis. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20255","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T19:09:09Z","timestamp":1086635349000},"page":"198-205","source":"Crossref","is-referenced-by-count":37,"title":["Anticancer agent CHS 828 suppresses nuclear factor\u2010\u03baB activity in cancer cells through downregulation of IKK activity"],"prefix":"10.1002","volume":"111","author":[{"given":"Lone Stengelsh\u00f8j","family":"Olsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille\u2010Julia 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