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Monomethyl auristatin F (MMAF) is an anti-mitotic agent that inhibits cell division by blocking the polymerization of tubulin. It is a new auristatin derivative ith a charged C-terminal phenylalanine residue that attenuates its cytotoxic activity compared to its uncharged counterpart MMAE. Because of its super toxicity, it cannot be used as a drug itself. It is linked to a monoclonal antibody (mAb) that directs it to the cancer cells. The linker to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the anti-mitotic mechanism.

Reference:

1. 1. Smith LM, et al. Potent cytotoxicity of an auristatin-containing antibody-drug conjugate targeting melanoma cells expressing melanotransferrin/p97. (2006)  Mol Cancer Ther. 5(6):1474-82
2. 2. Doronina, SO, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. (2006) Bioconjug Chem, 17(1):114-24.
3. 3. Oflazoglu E, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. (2008) Clin Cancer Res. 14(19):6171-80.
4. 4. Nilsson R, et al. Toxicity-reducing potential of extracorporeal affinity adsorption treatment in combination with the auristatin-conjugated monoclonal antibody BR96 in a syngeneic rat tumor model. (2010) Cancer 116(4 Suppl):1033-42.
5. 5. http://en.wikipedia.org/wiki/Monomethyl_auristatin_E

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