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.
MeSH terms
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Androstadienes / chemistry*
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Androstadienes / pharmacology
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / chemical synthesis*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cetuximab
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Cross-Linking Reagents
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Drug Design*
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Drug Synergism
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Humans
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Immunoconjugates
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Immunosuppressive Agents / chemical synthesis
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Inhibitory Concentration 50
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Wortmannin
Substances
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Androstadienes
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Cross-Linking Reagents
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Immunoconjugates
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Immunosuppressive Agents
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Cetuximab
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Wortmannin