The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 18, 2025

The ribosomal DNA (rDNA) plays a vital role in regulating protein synthesis by ribosome biogenesis, essential for maintaining cellular growth, metabolism, and more. Cancer cells show high dependence on biogenesis exhibit elevated rDNA transcriptional activity. CX-5461, also known as Pidnarulex, is First-in-Class anticancer drug that has received 'Fast Track Designation' approval from the FDA. Initially reported to inhibit Pol I-driven transcription, CX-5461 was recently identified G-quadruplex structure (G4) stabilizer currently completed or undergoing multiple Phase I clinical trials patients with breast ovarian cancers harboring BRCA1/2, PALB2, other repair deficiencies. Additionally, preclinical studies have confirmed demonstrates promising therapeutic effects against multifarious non-cancer diseases, including viral infections, autoimmune diseases. This review summarizes mechanisms of its inhibition rDNA, binding G4, toxicity towards topoisomerase, along research status across various Lastly, this highlights targeted therapy strategy based nanomedicine delivery, particularly delivery utilizing nucleic acid aptamer AS1411, which contains G4 motif specifically target highly expressed nucleolin surface tumor cell membranes; It anticipates coupling peptide acids locked achieve dual targeting, thereby realizing individualized G4-targeting CX-5461. aims provide general overview progress recent years suggest potential strategies disease treatment involving RNA synthesis, topoisomerase.

Language: Английский

G-quadruplex in cancer energy metabolism: A potential therapeutic target

Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2025, Volume and Issue: unknown, P. 130810 - 130810

Published: April 1, 2025

Language: Английский