TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor

• Published in: Molecular cancer therapeutics Vol. 21; no. 7; pp. 1090 - 1102
• Main Authors: Jo, Ukhyun, Murai, Yasuhisa, Agama, Keli K., Sun, Yilun, Saha, Liton Kumar, Yang, Xi, Arakawa, Yasuhiro, Gayle, Sophia, Jones, Kelli, Paralkar, Vishwas, Sundaram, Ranjini K., Van Doorn, Jinny, Vasquez, Juan C., Bindra, Ranjit S., Choi, Woo Suk, Pommier, Yves
• Format: Journal Article
• Language: English
• Published: United States 05.07.2022
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - metabolism; Camptothecin - analogs & derivatives; DNA - metabolism; DNA Topoisomerases, Type I - metabolism; Humans; Mice; Neoplasms - drug therapy; Neoplasms - genetics; Nuclear Proteins - metabolism; Protein Kinase Inhibitors - pharmacology; Topoisomerase I Inhibitors - pharmacology

Exatecan and deruxtecan are antineoplastic camptothecin derivatives in development as tumor-targeted-delivery warheads in various formulations including peptides, liposomes, polyethylene glycol nanoparticles, and antibody–drug conjugates. Here, we report the molecular pharmacology of exatecan compar...