Recent Update on Targeting c-MYC G-Quadruplexes by Small Molecules for Anticancer Therapeutics

Guanine-rich DNA sequences have the propensity to adopt four-stranded tetrahelical G-quadruplex (G4) structures that are overrepresented in gene promoters. The structural polymorphism and physicochemical properties of these non-Watson-Crick G4 structures make them important targets for drug development. The guanine-rich nuclease hypersensitivity element III₁ present in the upstream of P1 promoter of c-MYC oncogene has the ability to form an intramolecular parallel G4 structure. The G4 structure that forms transiently in the c-MYC promoter functions as a transcriptional repressor element. The c-MYC oncogene is overexpressed in a wide variety of cancers and plays a key role in cancer progression. Till now, a large number of compounds that are capable of interacting and stabilizing thec-MYC G4 have been reported. In this review, we summarize various c-MYC G4 specific molecules and discuss their effects on c-MYC gene expression in vitro and in vivo.