Chemically programmed antibodies: Endothelin receptor targeting CovX-Bodies

β-Diketone containing aryl sulfonamide endothelin antagonists were synthesized and covalently linked to the reactive lysine of the antibody m38C2 to create a series of chemically programmed antibodies. These antibodies, named as CovX-Bodies, behaved as potent endothelin receptor antagonists in vitro...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-01, Vol.17 (2), p.501-506
Main Authors: Doppalapudi, Venkata R., Tryder, Nancy, Li, Lingna, Aja, Teresa, Griffith, David, Liao, Francesca-Fang, Roxas, Giovanni, Ramprasad, Mysore P., Bradshaw, Curt, Barbas, Carlos F.
Format: Article
Language:English
Subjects:
Aldolase antibody
Animals
Antibodies - chemistry
Antibodies - pharmacology
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Antitumor efficacy
Biological and medical sciences
CHO Cells
CovX-Body
Cricetinae
Cricetulus
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists
Endothelin-A
Endothelin-A (ET A) antagonists
General aspects
Humans
Indicators and Reagents
Medical sciences
Mice
Mice, Nude
Molecular Conformation
Monoclonal antibodies
Neoplasm Transplantation
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Endothelin - drug effects
Structure-Activity Relationship
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Description
Summary:β-Diketone containing aryl sulfonamide endothelin antagonists were synthesized and covalently linked to the reactive lysine of the antibody m38C2 to create a series of chemically programmed antibodies. These antibodies, named as CovX-Bodies, behaved as potent endothelin receptor antagonists in vitro and showed anti-tumor effect in vivo. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.10.009