Sudemycin E0

Sudemycin E0 is a synthetic analog of spliceosome inhibitors and a potent ADC cytotoxin used as an ADC payload in antibody-drug conjugates. Its mechanism of action involves selective inhibition of the SF3b subunit of the spliceosome, disrupting pre-mRNA splicing, leading to accumulation of unprocessed transcripts and induction of apoptosis in proliferating tumor cells. Its chemical structure allows efficient conjugation to antibodies via cleavable or non-cleavable linker chemistries for targeted intracellular delivery.

Within antibody-drug conjugates, Sudemycin E0 is linked to monoclonal antibodies through linkers that ensure systemic stability and controlled payload release within target cells. The ADC remains inactive during circulation and releases Sudemycin E0 upon internalization and enzymatic processing, allowing selective cytotoxic activity in tumor cells expressing the targeted antigen. This approach supports precise delivery of spliceosome inhibition to malignant cells while minimizing off-target effects.

Applications of Sudemycin E0 include its integration into ADCs targeting both hematologic malignancies and solid tumors. Its chemical compatibility with diverse linker systems facilitates optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic profiles. Sudemycin E0 demonstrates reproducible cytotoxicity in spliceosome-dependent cancer cells, enabling the development of ADCs with well-defined mechanisms of action and targeted antitumor activity.