Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 11, Pages 3642-3646Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201510866
Keywords
antitumor agents; cell recognition; drug design; immunology; medicinal chemistry
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Funding
- Bristol-Myers Squibb [OCR4997.11]
- NRF [2013R1A2A2A01067638, 2012M3C1A6035362]
- National Research Foundation of Korea [2013R1A2A2A01067638] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 invivo 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.
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