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

The MYC–MAX heterodimer interface is a critical protein-protein interaction (PPI) between the Myc proto-oncogene protein (MYC) and its obligate partner, Myc-associated factor X (MAX) [1, 2]. This heterodimerization is essential for MYC to bind to DNA at E-box sequences and regulate the transcription of thousands of genes involved in cell growth, proliferation, metabolism, and apoptosis [1, 3]. In many human cancers, MYC is overexpressed or deregulated, driving oncogenesis and tumor maintenance, making the MYC–MAX interface a high-priority therapeutic target [3, 4]. Historically considered "undruggable" due to its disordered structure and lack of a traditional small-molecule binding pocket, recent advances have identified small molecules and peptides that disrupt this interface [5, 6]. These inhibitors prevent the formation of the active transcription factor complex, thereby suppressing the expression of MYC-driven oncogenic programs [7]. Clinical development of such agents, including the mini-protein OMO-103, aims to treat a wide range of solid and hematological malignancies [8]. However, challenges remain regarding the potential impact on normal regenerative tissues where MYC plays a physiological role [9]. [1] Dang CV. Cell. 2012;149(1):22-35. [2] Amati B, et al. Curr Opin Genet Dev. 1994;4(1):102-8. [3] Meyer N, Penn LZ. Nat Rev Cancer. 2008;8(12):976-90. [4] Whitfield JR, et al. Expert Opin Ther Targets. 2017;21(10):915-924. [5] McKeown MR, Bradner JE. Cold Spring Harb Perspect Med. 2014;4(10):a014266. [6] Beaulieu ME, et al. Sci Rep. 2019;9(1):10327. [7] Han H, et al. Future Med Chem. 2020;12(4):297-311. [8] Garralda E, et al. Ann Oncol. 2022;33(suppl_7):S197-S198. [9] Soucek L, et al. Nature. 2008;455(7213):679-83.

Other names

c-Myc/Max complexMYC/MAX heterodimerMYC-MAX protein-protein interactionMYC-MAX PPI

Disruption of protein-protein interaction (PPI) between MYC and MAX, preventing DNA binding and transcriptional activation.