Drug-Linker Constructs Bearing Unique Dual-Mechanism Tubulin Binding Payloads Tethered through Cleavable and Non-Cleavable Linkers.

ABSTRACT: Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels. These payloads have been incorporated into a variety of drug-linker constructs utilizing the clinically relevant cathepsin B cleav

SUBMITTER: Ford JW 

PROVIDER: S-EPMC11722312 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature