A Promising but Challenging Strategy for Cancer Treatment: Disruption of Myc-Max Heterodimerization

Hyojin Kim,Kwan-Young Jung,Minjin Yoo

doi:10.15344/2456-3501/2016/114

Abstract

c-Myc (Myc) is oncoprotein and nuclear transcription factor which plays a crucial role in several central cellular processes, involving cell proliferation, transformation, inhibition of differentiation and apoptosis. These functions result from the transcriptional activity of Myc. To be a functional form, Myc protein binds to the Max which recruits the E-box. Dysregulated over-expression of Myc is observed in many human malignancies including breast cancer, small-cell lung cancer, osteosarcomas, glioblastomas, and myeloid leukemias. Therefore, inhibition of the Myc-Max dimerization is a promising strategy for anticancer therapy. In this review, we summarize the Myc-Max disruption by small molecules targeting the oncogene. These information will contribute to the research and development of Myc-targeted smallmolecule drugs.

Highlights

Cancer is one of the most feared of all human diseases, and the need to develop high-efficacy and low-toxicity cancer drugs is an important field that is being actively studied
Myc is a transcriptional regulator with a basic helix-loop-helix leucine zipper domain that becomes functional after dimerization with its obligate partner protein, Max [2]
Overexpression of Myc is involved in transformation processes, including proliferation, apoptosis, differentiation, and metabolism [5]; dysregulation of Myc is involved in the vast majority of human cancers such as lung, pancreatic, and colorectal cancer in addition to leukemia and lymphomas [6]

Summary

Introduction

Cancer is one of the most feared of all human diseases, and the need to develop high-efficacy and low-toxicity cancer drugs is an important field that is being actively studied. Because of its multiple functions, there has been concern that targeting Myc-Max/DNA interactions for drug development would result in undesirable side effects. In a follow-up modification, N-methylpiperidinyl functionalization of the rhodanine NH group followed by substitution with an isopropylphenyl ring resulted in the introduction of 28RHNCN-1 and inhibition of Myc binding to DNA that is equivalent to 10058-F4 in an in vitro system.

Results

Conclusion