sulfo-DGN462 sodium

Sulfo-DGN462 sodium is a synthetic duocarmycin-based compound and a potent ADC cytotoxin used as an ADC payload in antibody-drug conjugates. Its cytotoxic mechanism involves sequence-selective alkylation of DNA in the minor groove, leading to stabilization of DNA duplexes, inhibition of replication, and induction of apoptosis in rapidly proliferating tumor cells. The sulfonated sodium form enhances solubility and chemical stability, facilitating efficient conjugation to monoclonal antibodies via cleavable or non-cleavable linker chemistries for controlled intracellular delivery in ADC applications.

Within antibody-drug conjugates, sulfo-DGN462 sodium is covalently linked to antibodies using linker systems engineered to maintain stability in systemic circulation while allowing selective payload release inside target cells. The ADC remains inactive during circulation to minimize off-target cytotoxicity. Upon receptor-mediated internalization into antigen-expressing tumor cells, enzymatic or chemical cleavage releases the active payload. Once liberated, sulfo-DGN462 sodium binds to DNA within the nucleus, causing replication arrest and triggering apoptosis. This targeted mechanism ensures cytotoxic activity is restricted to tumor cells, enhancing specificity and reproducibility of tumor-targeted therapy.

Applications of sulfo-DGN462 sodium include incorporation into ADCs targeting both hematologic malignancies and solid tumors with defined antigen expression. Its chemical compatibility with diverse linker chemistries allows optimization of conjugation efficiency, intracellular release kinetics, and pharmacokinetic profiles. Preclinical studies demonstrate potent cytotoxicity in target-expressing tumor cells. Sulfo-DGN462 sodium supports the development of ADCs with controlled DNA-alkylating activity, providing mechanistically precise apoptosis induction and tumor cell elimination, facilitating rational design of antibody-drug conjugates for targeted oncology applications.