Synthesis and biological evaluation of thiosemicarbazone-based antibody-drug conjugates.

ABSTRACT: Metal chelators belonging to the di-pyridyl-thiosemicarbazone (DpTs) class have shown great promise as adjuvant therapeutics for treating cancer, with DpC and Dp44mT emerging as the lead candidates. Despite their efficacy, these molecules also induce various undesirable side effects due to insufficient cancer cell targeting, highlighting the need to improve their selectivity. Here, we present a first generation of DpT-antibody conjugates. To this end, we developed a facile synthesis to functionalize DpTs strategically with click-able azido linkers. Moreover, selective side-chain modification of the clinical antibody trastuzumab (Tras) with a complementary bis-alkyne moiety is described. Using this new chemistry, we conjugated four different azido DpTs to trastuzumab via a combinatio

SUBMITTER: Sheernaly N 

PROVIDER: S-EPMC12198877 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature