Abstract
Aryl sulfonamide-based endothelin antagonists were synthesized and covalently linked to the reactive lysine of the m38C2 antibody to create a series of CovX-Bodies. These chemically programmed antibodies behaved as potent endothelin receptor antagonists in vitro and had antitumor efficacy in a prostate cancer xenograft model which, on a molar basis, far exceeded the activity of the parent small molecule.
MeSH terms
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Animals
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Antibodies / chemistry*
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Antibodies / pharmacology*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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CHO Cells
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Cricetinae
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Cricetulus
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Endothelin A Receptor Antagonists
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Endothelin B Receptor Antagonists
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Humans
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Indicators and Reagents
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Mice
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Mice, Nude
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Molecular Conformation
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Neoplasm Transplantation
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Receptors, Endothelin / drug effects*
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Structure-Activity Relationship
Substances
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Antibodies
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Antineoplastic Agents
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Endothelin A Receptor Antagonists
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Endothelin B Receptor Antagonists
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Indicators and Reagents
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Receptors, Endothelin