A wortmannin-cetuximab as a double drug.
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.
Smith
R Adam
RA
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA.
Yuan
Hushan
H
Weissleder
Ralph
R
Cantley
Lewis C
LC
Josephson
Lee
L
D000730:Androstadienes / Q000737:chemistry* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D003432:Cross-Linking Reagents; D015195:Drug Design; D004357:Drug Synergism; D006801:Humans; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000138:chemical synthesis; D020128:Inhibitory Concentration 50; D000077191:Wortmannin
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000068818:Cetuximab; D000077191:Wortmannin