Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.

ABSTRACT: A strategy for targeting tumor-associated hypoxia utilizes reductase enzyme-mediated cleavage to convert biologically inert prodrugs to their corresponding biologically active parent therapeutic agents selectively in areas of pronounced hypoxia. Small-molecule inhibitors of tubulin polymerization represent unique therapeutic agents for this approach, with the most promising functioning as both antiproliferative agents (cytotoxins) and as vascular disrupting agents (VDAs). VDAs selectively and effectively disrupt tumor-associated microvessels, which are typically fragile and chaotic in nature. VDA treatment may augment existing tumor-associated hypoxia, thus enhancing the efficacy of hypoxia-selective prodrugs. Structure activity relationship-guided studies in our laboratories led to the di

SUBMITTER: Shi Z 

PROVIDER: S-EPMC12416921 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature