NF-κB activation in HAM/TSP is inhibited by PBS-1086, a novel inhibitor of NF-κB. The potency and selectivity of several small-molecule inhibitors of NF-κB were assessed using the NF-κB DNA-binding ELISA (A-B) and a 293/NF-κB–luciferase reporter cell line (C). (A) Percent inhibition of RelA binding as a function of inhibitor concentration (μM) for parthenolide, DHMEQ, and PBS-1086. (B) Percent inhibition of RelB binding as a function of inhibitor concentration (μM) for parthenolide, DHMEQ, and PBS-1086. (C) Percent inhibition of luciferase activity in TNF-α–treated 293/NF–κB-luciferase reporter cell line as a function of inhibitor concentration (μM) for PBS-1086 and its regioisomer PBS-1143. The efficacy of DHMEQ and PBS-1086 at inhibiting NF-κB activation in HAM/TSP PBMCs was tested using the NF-κB DNA-binding ELISA. (D) RelA-, RelB-, and c-Rel–binding activity in nuclear extracts from untreated, DMSO (vehicle), DHMEQ (10μM)–, or PBS-1086 (10μM)–treated HAM/TSP PBMCs (n = 6). **P < .01, ANOVA and Dunnett posttest.