10058-F4

Background

The small-molecule 10058-F4 inhibits c-Myc, a transcriptional regulator involved in cell proliferation, differentiation, and apoptosis. Dysregulation of the oncoprotein c-Myc is common in human cancers. 10058-F4 inhibits transactivation of gene expression by c-Myc-Max heterodimers by disrupting the association between c-Myc and the transcription factor Max (1). 10058-F4 treatment of acute myeloid leukemia cells inhibited c-Myc expression and induced apoptosis and cell arrest at G0/G1 (2). In a mouse neuroblastoma model, 10058-F4 inhibited transactivation by N-Myc-Max, resulting in cell cycle arrest, apoptosis, and tumor growth reduction (3). Ovarian cancer cells treated with 10058-F4 displayed reduced cell proliferation and enhanced effects of chemotherapeutic drugs. The 10058-F4 inhibitor likely upregulates FOXO transcription factors and downstream genes involved in ovarian G1 cell cycle arrest, apoptosis, and autophagic cell death (4). 10058-F4 promoted increased expression of thioredoxin-interacting protein (TXNIP) in triple-negative breast cancer drug-resistant cells, which promoted reactive oxygen species synthesis and reversed doxorubicin-induced chemotherapy resistance (5).