Horizon Omics Biotechnology (Changchun) Co., Ltd. published the article titled "A Synthetic Lethal Approach to Drug Targeting of G-Quadruplexes Based on CX-5461" in 2023. G-quadruplex (G4) structures are enriched in cancer genomes, and drug development targeting G4 structures has a history of over 20 years. CX-3543 (Tetrafluorosine) was the first G4-targeting drug to enter clinical trials in 2005; however, it was withdrawn from Phase II clinical trials due to a lack of efficacy. Another G4-stabilizing drug, CX-5461 (Pidnarulex), also showed efficacy issues in clinical trials involving patients with advanced hematologic malignancies. It wasn’t until 2017, when the synthetic lethal (SL) interaction between Pidnarulex and the BRCA1/2-mediated homologous recombination (HR) pathway was discovered, that the drug achieved promising clinical efficacy.
