{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:28:18Z","timestamp":1773307698003,"version":"3.50.1"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"32","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Nuclear Factor-Kappa B (NF-\u03baB) is a transcription factor whose inappropriate activation may result in the development of a number of diseases including cancer, inflammation, neurodegeneration and AIDS. Recent studies on NF- \u03baB mediated pathologies, made therapeutic interventions leading to its inhibition an emerging theme in pharmaceutical research. NF-\u03baB resides in the cytoplasm and is activated by several time-dependent factors, leading to proteasomedependent degradation of its inhibitory protein (I\u03baB), resulting in free NF-\u03baB (p50 and p65 subunits, involved in disease states), which binds to target DNA sites, further resulting in enhanced transcription of several disease associated proteins. The complex pathway of NF-\u03baB, finally leading to its DNA binding, has attracted several approaches interfering with this pathway. One such approach is that of a direct covalent modification of NF-\u03baB. In this article, we present a critical review of the pharmacological agents that have been studied as inhibitors of NF-\u03baB by covalently modifying redox-regulated cysteine residues in its subunits, ultimately resulting in the inhibition of \u03baB DNA recognition and binding. Beginning with a general overview of NF-\u03baB pathway and several possibilities of chemical interventions, the significance of redoxregulation in NF-\u03baB activation and DNA binding is presented. Further, protein S-thiolation, S-nitrosylation and irreversible covalent modification are described as regular biochemical events in the cell, having provided a guideline for the development of NF-\u03baB inhibitors discussed further. Although just a handful of inhibitors, with most of them being alkylating agents have been studied in the present context, this approach presents potential for the development of a new class of NF-\u03baB-inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2174\/092986709789578222","type":"journal-article","created":{"date-parts":[[2009,10,10]],"date-time":"2009-10-10T16:34:09Z","timestamp":1255192449000},"page":"4261-4273","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Direct Covalent Modification as a Strategy to Inhibit Nuclear Factor-Kappa B"],"prefix":"10.2174","volume":"16","author":[{"given":"V.","family":"Pande","sequence":"first","affiliation":[]},{"given":"S. F.","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"M. J.","family":"Ramos","sequence":"additional","affiliation":[{"name":"REQUIMTE, Departamento de Quimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.,Portugal"}]}],"member":"965","container-title":["Current Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/092986709789578222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/70249\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/092986709789578222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T08:17:24Z","timestamp":1761380244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/70249\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11]]},"references-count":0,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2009,11]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/092986709789578222","relation":{},"ISSN":["0929-8673"],"issn-type":[{"value":"0929-8673","type":"print"}],"subject":[],"published":{"date-parts":[[2009,11]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-11-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}