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.

Graphical abstractβ-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.Figure optionsDownload full-size imageDownload as PowerPoint slide