Monomethyl auristatin E

Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. It is part of the auristatin family, which are microtubule-disrupting agents derived from the marine shell-less mollusk Dolabella auricularia. MMAE is a potent cytotoxin that is used as a conjugate in antibody-drug conjugates (ADCs) for the treatment of various types of cancer.

Chemistry

MMAE is a synthetic derivative of dolastatin 10, a natural product isolated from the sea hare. It is a potent inhibitor of cell division and protein synthesis, with a mechanism of action similar to that of vinca alkaloids. MMAE inhibits tubulin polymerization, leading to G2/M phase cell cycle arrest and subsequent apoptosis (programmed cell death).

Pharmacology

MMAE is not used as a standalone drug, but is linked to a monoclonal antibody via a linker to form an ADC. The antibody binds to specific antigens on the surface of cancer cells, delivering MMAE directly to the target cells. Once inside the cell, MMAE is released and binds to tubulin, disrupting the microtubule network and causing cell death.

Clinical use

MMAE is used in the form of ADCs for the treatment of various types of cancer, including breast cancer, lung cancer, and lymphoma. The ADC brentuximab vedotin, which targets the CD30 antigen, is approved for the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Another ADC, polatuzumab vedotin, which targets the CD79b antigen, is approved for the treatment of diffuse large B-cell lymphoma.

Safety

As with other cytotoxic agents, MMAE can cause a number of side effects, including neutropenia, thrombocytopenia, anemia, fatigue, nausea, and vomiting. The risk of side effects can be reduced by carefully selecting patients for treatment and monitoring them closely during therapy.

See also

• Antibody-drug conjugate
• Auristatin
• Microtubule