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Targets of Ado-trastuzumab emtansine
Ado-trastuzumab emtansine is aHER2-targeting antibody-drug conjugate. The antibody is humanized anti-HER2 IgG1, trastuzumab. The small molecule cytotoxin DM1 is a microtubule inhibitor. Trastuzumabbinds to subdomain IV of the HER2 receptor and enters cells through receptor-mediated endocytosis. Lysosomes degradetrastuzumaband releaseDM1. DM1 binds to tubulin in microtubules and inhibits microtubule function producing cell arrest and apoptosis. Also, similar to trastuzumab, in vitro studies have shown that both inhibition of HER2 receptor signaling and antibody-dependent cellular cytotoxicity are mediated by trastuzumab.
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