Publication： Angewandte Chemie

Date of Publication: February 15, 2016

Authors： Anthony F. Rullo, Kelly J. Fitzgerald, Viswanathan Muthusamy, Min Liu, Cai Yuan, Mingdong Huang, Minsup Kim, Art E. Cho, and David A. Spiegel

DOI: 10.1002/anie.201510866

Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM-U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer.