c-MYC promoter G-quadruplex DNA (c-MYC G4) (c-MYC G4)

The c-MYC G-quadruplex DNA is a non-canonical secondary structure formed within the Nuclease Hypersensitive Element III1 (NHE III1) of the c-MYC oncogene promoter (Siddiqui-Jain et al., 2002, PNAS). This structure acts as a molecular switch that regulates the transcription of c-MYC, a master regulator of cell growth, proliferation, and metabolism (Brooks et al., 2010, Genes & Cancer). In many cancers, c-MYC is overexpressed, driving uncontrolled cellular division and survival (Balasubramanian et al., 2011, Nature Reviews Drug Discovery). Small molecules designed to stabilize this G-quadruplex structure effectively lock the promoter in an inactive state, preventing the assembly of the transcriptional machinery and reducing oncogene expression (Yang and Hurley, 2006, Molecular Cancer Therapeutics). Some advanced therapeutic strategies involve dual-targeting ligands that bind both the G-quadruplex and adjacent A-T rich minor groove regions to enhance binding affinity and selectivity over other genomic G-quadruplexes (Ou et al., 2008, Journal of Medicinal Chemistry). Despite its potential, targeting this region remains challenging due to the structural similarity between different G-quadruplexes across the genome and the need for high specificity to avoid systemic toxicity.

Other names

NHE III1 G-quadruplexMYC G4 DNAc-MYC Pu27 G-quadruplexc-MYC promoter nuclease hypersensitive element III1c-MYC G-quadruplex DNA / A-T rich minor groove regions

Stabilization of the G-quadruplex structure within the c-MYC promoter region to sterically inhibit transcription factor binding and RNA polymerase recruitment, leading to the downregulation of c-MYC oncogene expression (Siddiqui-Jain et al., 2002; Yang and Hurley, 2006).