Monomethylauristatin E
Monomethylauristatin E (MMAE) is a synthetic antineoplastic agent. It is part of the auristatin family, which are microtubule-disrupting agents. MMAE is a potent cytotoxin that is used as a conjugate in antibody-drug conjugates (ADCs) for the treatment of various types of cancer.
History[edit | edit source]
Monomethylauristatin E was first synthesized in the late 20th century as part of a series of compounds known as dolastatins, which were originally isolated from the sea hare Dolabella auricularia. The dolastatins were found to have potent antineoplastic activity, leading to the development of synthetic analogs such as MMAE.
Mechanism of Action[edit | edit source]
MMAE works by inhibiting cell division and thus preventing the growth of cancer cells. It does this by binding to tubulin, a protein that forms the microtubule structures within cells that are necessary for cell division. By disrupting these structures, MMAE prevents the cells from dividing, leading to cell death.
Use in Antibody-Drug Conjugates[edit | edit source]
MMAE is too toxic to be used as a standalone drug. However, it can be attached to a specific antibody that targets a particular type of cancer cell. This allows the MMAE to be delivered directly to the cancer cells, minimizing damage to healthy cells. This approach is used in ADCs such as brentuximab vedotin and polatuzumab vedotin, which are used to treat Hodgkin lymphoma and diffuse large B-cell lymphoma, respectively.
Side Effects[edit | edit source]
Like all antineoplastic agents, MMAE can cause side effects. These can include nausea, vomiting, fatigue, and hair loss. More serious side effects can include neutropenia, a decrease in white blood cells that can lead to an increased risk of infection.
See Also[edit | edit source]
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