Shin, Yongje Lim, Sang Min Yan, Hong Hua Jung, Sungwoo Fang, Zhenghuan Jung, Kyung Hee Hong, Soon-Sun Hong, Sungwoo 2024-01-20T03:01:34Z 2024-01-20T03:01:34Z 2021-09-04 2016-11-10 0223-5234 https://pubs.kist.re.kr/handle/201004/123445 Targeting I kappa B kinase beta (IKK beta) can be a promising strategy in the development of a therapeutic treatment of inflammatory diseases because IKK beta is well-recognized as a key mediator of the NF-kappa B signaling pathway. In this study, we have successfully developed a structure-activity relationship (SAR) profile of the aminopyrimidine-based IKK beta inhibitors through the structure-based design strategy to improve the physicochemical properties and cellular activity in terms of the anti-inflammatory effects. Representative compounds exhibited desirable activity in nitric oxide (NO) reduction by inhibiting the synthesis of inducible nitric oxide synthase (iNOS), and strongly inhibited the expression of pro-inflammatory cytokines (IL-1 alpha, IL-6, and TNF-alpha). The inhibitory effects of 8e on the phosphorylation in the NF-kappa B pathway further supported that the suppression of the NF-kappa B signaling pathway induced the anti-inflammatory effect in LPS-stimulated Raw 264.7 cells. (C) 2016 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER IKK-BETA DESIGN INFLAMMATION DISCOVERY VIVO Optimization and biological evaluation of aminopyrimidine-based I kappa B kinase beta inhibitors with potent anti-inflammatory effects Article 10.1016/j.ejmech.2016.07.075 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.123, pp.544 - 556 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 123 544 556 scie scopus 000385319000044 2-s2.0-84982844988 Chemistry, Medicinal Pharmacology & Pharmacy Article IKK-BETA DESIGN INFLAMMATION DISCOVERY VIVO IKK beta Inhibitor Structure-activity relationship NO reduction Anti-inflammatory effect