Abstract: PLXDC1 and PLXDC2 represent a new cell-surface receptor family (collectively referred to as PLXDC proteins). The present disclosure reports that Domain A of the PLXDC proteins functions as an inhibitory domain, as the deletion thereof activates PLXDC signaling. Antibodies and antigen-binding fragments that bind to Domain A can therefore relieve its inhibitory function and activate PLXDC signaling, leading to killing of endothelial cells in pathogenic blood vessel that express the PLXDC protein. Methods are described for efficient screening of PLXDC-activating antibodies that bind to Domain A. In particular, the method entails the use of a small molecule agent that binds the PLXDC protein, making Domain A more accessible to a test antibody. With the new method, antibodies that bind to Domain A and can activate PLXDC signaling have been successfully identified.

Abstract: The disclosure provides compounds, and compositions, including pharmaceutical compositions, kits that include the compounds, and methods of using (or administering) and making the compounds. The disclosure further provides compounds or compositions thereof for use in a method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenic blood vessels. The disclosure further provides compounds or compositions thereof for use in a method of treating a disease, disorder, or condition that is mediated, at least in part, by PEDF receptors or by angiogenesis.

Abstract: The disclosure provides compounds, and compositions, including pharmaceutical compositions, kits that include the compounds, and methods of using (or administering) and making the compounds. The disclosure further provides compounds or compositions thereof for use in a method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenic blood vessles. The disclosure further provides compounds or compositions thereof for use in a method of treating a disease, disorder, or condition that is mediated, at least in part, by PEDF receptors or by angiogenesis.