G-quadruplex ligands in cancer therapy: Progress, challenges, and clinical perspectives

Abstract

Guanine-rich sequences can form G-quadruplexes (G4) in living cells, making these structures promising anti-cancer targets. Compounds able to recognize these structures have been investigated as potential anticancer drugs; however, no G4 binder has yet been approved in the clinic. Here, we describe G4 ligands structure-activity relationships, in vivo effects as well as clinical trials. Addressing G4 ligand characteristics, targeting challenges, and structure-activity relationships, this review provides insights into the development of potent and selective G4-targeting molecules for therapeutic applications.

Keywords: Biological activity; Drug-DNA interactions; G-quadruplex ligand; Heterocycle compounds; Ligand design; Structure-activity relationship.