Abstract
Target identification of small molecules is a great challenge but an essential step in drug discovery. Here, a quantitative proteomics approach has been used to characterize the cellular targets of DR, a DDR1 inhibitor. By taking advantage of competitive affinity-based protein profiling coupled with bioimaging, Cathepsin D (CTSD) was found to be the principle off-target of DR in human cancer cells. Further findings suggest the potential of DR as a novel CTSD inhibitor for breast cancer treatment. In addition, a trans-cyclooctene (TCO) containing probe was developed to track the binding between DR and its target proteins in living systems and could be a useful tool for DDR1 detection.
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