Chemically programmed antibodies: endothelin receptor targeting CovX-Bodies.
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.
Doppalapudi
Venkata R
VR
CovX Research LLC, 9381 Judicial Drive, Suite 200, San Diego, CA 92130, USA. dvramana@covx.com
Tryder
Nancy
N
Li
Lingna
L
Aja
Teresa
T
Griffith
David
D
Liao
Francesca-Fang
FF
Roxas
Giovanni
G
Ramprasad
Mysore P
MP
Bradshaw
Curt
C
Barbas
Carlos F
CF
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D008819:Mice, Nude; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D017466:Receptors, Endothelin / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000906:Antibodies; D000970:Antineoplastic Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D007202:Indicators and Reagents; D017466:Receptors, Endothelin