Myc-Max complex (Myc-Max)

The Myc-Max complex is a heterodimeric transcription factor assembly consisting of the proto-oncoprotein Myc (c-Myc, N-Myc, or L-Myc) and its obligate partner, Myc-associated factor X (Max) [1, 4]. This complex binds to specific DNA sequences known as E-boxes (CACGTG) to regulate the expression of thousands of genes involved in cell growth, proliferation, metabolism, and apoptosis [5, 8]. In many human cancers, Myc is overexpressed or deregulated, leading to uncontrolled cellular expansion and metabolic reprogramming [7, 11]. Because Myc lacks a defined ligand-binding pocket and is intrinsically disordered, the Myc-Max interaction surface has historically been considered undruggable [1, 15]. However, therapeutic strategies now focus on small molecules or mini-proteins, such as Omomyc, that disrupt the dimerization of Myc and Max or prevent the complex from binding to DNA [2, 7]. Successful inhibition of this complex has shown promise in regressing tumors in various preclinical models, although concerns regarding the impact on rapidly dividing normal tissues remain a key consideration in clinical development [9, 15].

Other names

c-Myc/MaxMYC/MAXMyc-Max heterodimerMyc-Max-DNA complexMyc-associated factor X complex

Inhibition of Myc-Max dimerization, disruption of Myc-Max-DNA binding at E-box sequences, and promotion of Myc protein degradation.