monomethyl auristatin E

Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent and a highly potent antimitotic drug derived from dolastatins, peptides originally isolated from the marine mollusc Dolabella auricularia. MMAE acts by inhibiting cell division through blocking the polymerization of tubulin, thereby disrupting microtubule formation and inducing cell cycle arrest at the G2/M phase followed by apoptosis. Due to its extreme toxicity to normal cells as well as cancer cells, MMAE is not used directly as a therapeutic drug. Instead, it serves as the cytotoxic payload in antibody-drug conjugates (ADCs), where it is covalently linked via a protease-cleavable linker to monoclonal antibodies that target specific tumor-associated antigens. Upon internalization into target cancer cells and lysosomal degradation of the ADC complex, MMAE is released intracellularly to exert its cytotoxic effect selectively on malignant cells[1][3][4][8]. Several FDA-approved ADCs use MMAE as their payload (e.g., brentuximab vedotin for CD30+ lymphomas; enfortumab vedotin for urothelial carcinoma)[6][9].

Other names

MMAE peptideN-Methyl-L-valyl-N-[(1S,2R)-4-[(2S)-2-[(1R,2R)-3-[[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]amino]-1-methoxy-2-methyl-3 oxopropyl]-1-pyrrolidinyl]-2-methoxy 1-(1S)-1-methylpropyl]-4 oxobutyl]-N methyl-L-valinamide