Novel curcumin analogs, GO-Y030 and GO-Y078, are multitargeted agents with enhanced abilities for multiple myeloma

Background: Multiple myeloma remains an incurable malignancy despite of the recent approval of new molecular-targeted agents. The complex molecular mechanism, composed of various signal networks, including nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PBK)I/KT, Janus kinase (JAK)lsignal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (1RF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application. Materials and Methods: Growth-suppressive abilities of newly synthesized analogs, GO-Y030 and GO-Y078 were analyzed. Molecular-targeted abilities of the analogs for NF-κB, PI3K/AKT, JAK/STAT3, IRF4 pathways, as well as inhibition of interleukin-6 (IL-6) production, were also examined. Results: GO-Y030 and GO-Y078 were 7 to 12-fold more potent growth suppressors for myeloma cells, and 6- to 15-fold stronger inhibitors of NF-κB, PI3K/AKT, JAK/STAT3, and IRF4 pathways than curcumin. GO-Y78 also 14-fold more potently inhibited IL-6 production. Conclusion: GO-Y030 and GO-Y078 are potential therapeutic candidates with enhanced abilities for multiple myeloma.