rezetecan

Rezetecan (also known as HS-9265 or SHR9265) is an investigational, cytotoxic small-molecule payload used in antibody-drug conjugates (ADCs). Chemically, it is an exatecan-derived camptothecin derivative that acts as a DNA topoisomerase I inhibitor. Rezetecan is developed by Jiangsu Hengrui Pharmaceuticals and Hansoh Pharma, which are closely related companies. It serves as the cytotoxic warhead in several clinical-stage ADCs, including the HER2-targeted trastuzumab rezetecan (SHR-A1811), the B7-H3-targeted risvutatug rezetecan (HS-20093 / GSK5764227), the B7-H4-targeted mocertatug rezetecan (HS-20089 / GSK5733584), and the TROP-2-targeted tizetatug rezetecan (SHR-A1921). Upon internalization of the ADC and cleavage of the linker, rezetecan is released into the tumor cell, where it stabilizes topoisomerase I-DNA complexes, leading to DNA double-strand breaks, cell cycle arrest, and apoptosis. It also exhibits a strong bystander killing effect due to its high membrane permeability.

Other names

MC-Gly-Gly-Phe-Gly-(R)-Cyclopropane-Exatecanrezetecan