Comparative Study on Covalent and Noncovalent Endogenous Albumin-Binding β-Glucuronidase-Activated SN38 Prodrugs for Antitumor Efficacy

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 6, 2025

Albumin-binding prodrugs have been explored to overcome the limitations of small-molecule anticancer chemotherapy agents, such as inadequate physiological and pharmaceutical compatibility, well rapid renal clearance. Herein, we investigated two endogenous albumin-binding prodrugs, M-g-SN38 S-g-SN38, forming macromolecular conjugates. Both exhibited robust stability in murine human plasma, crucial for their therapeutic potential. Selective activation by β-glucuronidase ensures minimal toxicity inactive state. Notably, higher cellular uptake, a longer circulation half-life, enhanced tumor accumulation compared suggesting its greater potential improved antitumor efficacy. In vivo, significant activity, leading profound reduction and, many cases, marked depletion complete eradication all treated mice HCT116 xenograft model. Furthermore, also demonstrated pronounced efficacy BxPC-3 Together, these findings provide new insights development prodrugs.

Язык: Английский

Stimuli-Responsive Prodrugs with Self-Immolative Linker for Improved Cancer Therapy

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116928 - 116928

Опубликована: Сен. 30, 2024

Язык: Английский