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A Wortmannin-Cetuximab as a Double Drug

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2009

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American Chemical Society
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Smith, R. Adam, Hushan Yuan, Ralph Weissleder, Lewis C. Cantley, and Lee Josephson. 2009. “A Wortmannin−Cetuximab as a Double Drug.” Bioconjugate Chemistry 20 (11): 2185–89. https://doi.org/10.1021/bc900176a.

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Abstract

Double drugs are obtained when two pharmacologically active entities are covalently joined to improve potency. We conjugated the viridin Wm with a self-activating linkage to cetuximab and demonstrated the retention of immunoreactivity by the conjugate. Though cetuximab lacked a growth inhibitory activity against A549 cells, the Wm-cetuximab conjugate had an antiproliferative IC(50) of 155 nM in vitro. The chemistry of attaching a self-releasing Wm to clinically approved antibodies is general and, in selected instances, may yield antibody-based double drugs with improved efficacy.

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