MYC promoter G-quadruplex DNA (MYC G4 DNA)

The MYC promoter G-quadruplex (G4) DNA is a non-canonical secondary structure formed within the nuclease hypersensitive element III1 (NHE III1) of the c-MYC proto-oncogene promoter. This G-rich sequence can transition between a double-stranded form and a four-stranded G-quadruplex structure, which acts as a molecular switch to silence MYC transcription. In many cancers, MYC is constitutively overexpressed, driving uncontrolled cell proliferation, metabolism, and survival. Therapeutic strategies focus on using small molecules to stabilize the G-quadruplex structure, thereby preventing the transcriptional machinery from accessing the promoter and effectively downregulating MYC expression. While several G4-stabilizing ligands have been developed, achieving high selectivity for the MYC G4 over thousands of other potential G4 sites in the human genome remains a significant pharmacological challenge. Successful targeting of this DNA structure represents a potent approach to treating MYC-dependent malignancies that are otherwise difficult to target at the protein level.

Other names

MYC promoterNuclease hypersensitive element III1NHE III1MYC G-quadruplexc-MYC promoter G4IGD DNA (Internal G-quadruplex DNA)

Stabilization of the G-quadruplex structure within the MYC promoter to inhibit transcription of the MYC oncogene.