Myc proto-oncogene protein–MYC-associated factor X protein interface (MYC/MAX interface)

The MYC/MAX protein-protein interface is a therapeutic target defined by the interaction between MYC and MAX transcription factors, mediated by their conserved basic helix–loop–helix leucine zipper (bHLHLZ) domains. MYC requires MAX to bind DNA and regulate gene transcription, controlling cell proliferation, growth, apoptosis, and differentiation. Abnormal MYC/MAX dimerization, typically due to MYC overexpression or dysregulation, drives oncogenesis in many human cancers. Targeting this interaction—by disrupting dimer formation—can block MYC-dependent tumor growth. Mechanistically, the interface does not present well-defined ligand pockets, making direct inhibition difficult; nonetheless, peptide-based inhibitors (such as Omomyc) and small molecules are being developed to block the MYC/MAX interface or its DNA-binding activity. Direct MYC/MAX inhibitors are in preclinical development, with Omomyc demonstrating efficacy and low toxicity in animal models. The broad biological role of MYC, however, introduces safety and selectivity challenges for such therapeutics.

Other names

MYC-MAX dimerization interfaceMYC/MAX heterodimer interfaceMYC:MAX protein:protein interaction site

Dimerization disruption (e.g., Omomyc prevents MYC/MAX formation by acting as a competitive inhibitor); Transcriptional downregulation (blockade of MYC/MAX prevents DNA binding and gene activation); Bromodomain inhibition (JQ1 and similar agents indirectly suppress MYC function by affecting chromatin regulators)