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MMAD is a potent tubulin inhibitor, is a toxin payload in antibody drug conjugates (ADCs).

MMAD (Monomethyl Dolastatin 10) is coupled through a stable oxime-ligation process to yield several near-homogenous antibody-drug conjugates (ADCs) with a drug-to-antibody ratio of ~2.0. The resulting conjugates demonstrate good pharmacokinetic properties, potent in vitro cytotoxic activity against HER2+ cancer cells. When compared with ADCs prepared by cysteine alkylation following native interchain disulfide reduction, site-specific unnatural-amino-acid-based ADCs are shown to have increased in vitro cytotoxicity.

The resulting antibody-drug conjugates (ADCs) demonstrate complete tumour regression in rodents. They also have an improved toxicology profile in rats.

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