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Overview
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Background
MMAD is a highly potent inhibitor of tubulin [1].MMAD is one of the auristatins, which are used as the drugs of antibody drug conjugates (ADCs). In ADCs, the therapeutic compounds and the high selectivity of antibodies are combined by the linkers. By taking advantage of antigen-selectivity of MAbs, it can deliver these cytotoxic drugs to antigen-expressing tumor cells, thus increasing both the efficacy and safety of therapy. As a payload of ADCs, MMAD is used to target the tubulin of the tumor cells. It can interfere with tubulin polymerization and induce rapid cell death at low picomolar concentrations [1]. Additionally, MMAD is reported to be used in the production of site-specific antibody drug conjugates (NDCs). In the NDCs, MMAD is combined with anti-5T4 antibody or anti-Her2 antibody. It is shown that the NDCs demonstrate better efficacy and pharmacokinetics [2].
[1] Puja Sapra, Andrea T Hooper, Christopher J, O’Donnell & Hans-Peter Gerber. Investigational antibody drug conjugates for solid tumors. Expert Opin. Investig. Drugs. 2011, 20(8):1131-1149.
[2] Feng Tiana, Yingchun Lu, Anthony Manibusan, Aaron Sellers et al. A general approach to site-specific antibody drug conjugates. PNAS. 2014, February, 111(5): 1766-1771.
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