Thiol-Michael addition based conjugate for glutathione activation and release

Glutathione (GSH) level has long been recognized as a valuable tumor biomarker. GSH-mediated activation and release systems have been extensively developed for cancer diagnosis and treatment, but mainly focused on disulfide-based conjugate. We reported here a new thiol-Michael addition based GSH response conjugate TC6, which consists of a unique tricyclic structure containing alpha, beta-unsaturated ketone responsive groups. The conjugate was easily synthesized and showed good selectivity to glutathione with certain stability. The camptothecin delivery experiment of TC6 showed improved anti-tumor ability in cells and tumor-bearing mice. TC6 could be used for the development of antibody or small molecule conjugated drugs.

Automated summary

Glutathione (GSH) level is an important tumor biomarker, and the newly discovered GSH response conjugate TC6 showed good stability and selectivity, and exhibited improved anti-tumor ability in cancer treatment. This finding provides a new direction for the development of anti-tumor drugs.