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Overview
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Background
SC-514 is a cell-permeable and selective inhibitor of IKK-2 with IC50 value of 3-12μM [1, 2].SC-514 inhibits all forms of recombinant human IKK-2 with IC50 values in the 3–12μM range. It also inhibits the native IKK complex. SC-514 specifically binds at the ATP-binding site of IKK-2 and exerts a reversible and competitive inhibition with ATP. However, SC-514 shows non-competitive inhibition with the IκB site. As an inhibitor of IKK-2, SC-514 is found to block the phosphorylation and degradation of IκBα and reduce the translocation level of p65 into the nucleus in IL-1β-treated RASFs. Additionally, SC-514 shows dose-dependent inhibition in the transcription of NF-κB-induced genes, including IL-6, IL-8, and COX-2. Moreover, SC-514 shows efficacious in reduction of LPS-induced TNFα production in the acute model of inflammation. SC-514 is also reported to inhibit the osteoclastogenesis in BMM cells through attenuating RANKL-induced activation of NF-κB [1, 2].
[1] Kishore N, Sommers C, Mathialagan S, Guzova J, Yao M, Hauser S, Huynh K, Bonar S, Mielke C, Albee L, Weier R, Graneto M, Hanau C, Perry T, Tripp CS. A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J Biol Chem. 2003 Aug 29;278(35):32861-71.
[2] Liu Q, Wu H, Chim SM, Zhou L, Zhao J, Feng H, Wei Q, Wang Q, Zheng MH, Tan RX, Gu Q, Xu J, Pavlos N, Tickner J, Xu J. SC-514, a selective inhibitor of IKKβ attenuates RANKL-induced osteoclastogenesis and NF-κB activation. Biochem Pharmacol. 2013 Dec 15;86(12):1775-83.
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