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

Tubulin^[1]

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^[1].

The resulting antibody-drug conjugates (ADCs) demonstrate complete tumour regression in rodents. They also have an improved toxicology profile in rats^[1].

• [1]. Chudasama V, et al. Recent advances in the construction of antibody-drug conjugates. Nat Chem. 2016 Feb;8(2):114-9.