JSH-23 HCl is designed as an inhibitor of NF-κB transcriptional activity with IC50 of 7.1 μM in RAW 264.7 cell line. JSH-23 inhibits NF-κB transcriptional activity in a dose-dependent manner in LPS-stimulated macrophages RAW 264.7. This effect is not due to its cytotoxicity. In the same condition, JSH-23 is found to significantly decrease the LPS-induced DNA binding activity of NF-κB while decrease nuclear amount of NF-κB p65. JSH-23 plays these roles without affecting IκB degradation. In addition, JSH-23 also shows inhibition effects on the expression of the pro-inflammatory transcripts and enzymes, including IL-6, IL-1β, COX-2 and TNF-α. Furthermore, JSH-23 inhibits LPS-induced apoptotic chromatin condensation.