mertansine
Overview
Mertansine (DM1; N2’-deacetyl-N2’-(3-mercapto-1-oxopropyl)-maytansine) is a potent maytansinoid microtubule-depolymerizing agent derived from maytansine. It is used as the cytotoxic warhead in antibody-drug conjugates, most notably ado-trastuzumab emtansine (T-DM1/Kadcyla). Free mertansine is not used as a standalone clinical agent due to narrow therapeutic index; its activity is harnessed via targeted ADC delivery.
Evidence in the corpus
- Free mertansine IC50 was ~10 nM across cancer cell lines regardless of ERBB2 (HER2) expression status, confirming indiscriminate cytotoxic potency that the ADC format must restrict through receptor-targeted delivery PMID:27698471.
- Free mertansine radiosensitizes tumour cells indiscriminately (both HER2+ and HER2− lines), in contrast to the ADC T-DM1, which only radiosensitizes HER2+ cells — establishing that receptor-mediated endocytosis and intracellular DM1 release, not free payload, is the mechanistic driver of T-DM1 radiosensitization PMID:27698471.
- The non-cleavable thioether linker (SMCC) in T-DM1 delivers mertansine as a lysine-DM1 catabolite after lysosomal processing; the paper notes that the MC-VC linker used in MMAE-based ADCs undergoes slow retro-Michael release but the SMCC linker used for DM1 has different stability properties PMID:27698471.
Resistance mechanisms
- Not reported in corpus.
Cancer types (linked)
- Not reported in corpus (free mertansine is a preclinical reference compound only).
Sources
This page was processed by entity-page-writer on 2026-04-15.