Novel c-Myc G4 stabilizer EP12 promotes myeloma cytotoxicity by disturbing NF-κB signaling

Abstract

Multiple myeloma (MM) is a B-cell malignancy characterized by the excessive proliferation of bone marrow plasma cells and the production of abnormal immunoglobulins. Despite advances in therapeutic strategies, it remains an incurable disease. Recently, innovative anticancer drugs have been developed and approved, leading to improvements in MM therapy; however, drug resistance continues to be a major obstacle that results in treatment failure. Therefore, the development of novel agents is imperative to achieve superior therapeutic outcomes for relapsed/refractory multiple myeloma (MM) patients. Previously, we identified EP12 as a c-Myc G4 stabilizer that could induce cytotoxicity in MM cells in vitro. However, further investigation is required to elucidate the underlying molecular mechanisms and anti-MM activity of EP12 in vivo. In this study, we have discovered that the compound EP12 effectively inhibits primary myeloma growth in vivo by destabilizing c-Myc and disrupting the canonical nuclear factor-κB (NF-κB) signaling pathway. Overall, our findings suggest that EP12, as a potent c-Myc inhibitor, holds great promise as a therapeutic agent for MM.

Keywords: EP12; Multiple myeloma; NF-κB signaling; c-Myc G4.