Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells

Abstract

Increasing evidence shows that c-Myc oncoprotein is tightly associated with multiple myeloma (MM) progression. Herein, we identified compound 7594-0035, which is a novel inhibitor that specifically targets c-Myc. It was identified from the ChemDiv compound database by molecular docking-based, high-throughput virtual screening. Compound 7594-0035 inhibited MM cell proliferation in vitro, induced cell cycle G2-phase arrest, and triggered MM cell death by disturbing the stability of c-Myc protein. Additionally, we also found that compound 7594-0035 overcame bortezomib (BTZ) drug resistance and increased the killing effect on MM cells in combination with BTZ. The severe combined immune deficiency (SCID) mouse xenograft model revealed that compound 7594-0035 partially decreased the primary tumor growth of Roswell Park Memorial Institute (RPMI)-8226 cells in vivo. The novel small molecular compound 7594-0035 described in the present study that targets c-Myc protein is likely to be a promising therapeutic agent for relapsed/refractory MM.