The development of small-molecule inhibitors targeting CD47

Immunotherapy has become an indispensable part of cancer treatment. A pivotal phagocytosis checkpoint, named cluster of differentiation 47 (CD47), which functions as 'don't eat me' signal to protect cells from phagocytosis upon interaction with signal regulatory protein alpha (SIRPa) on macrophages, has recently attracted much attention. Numerous antibodies targeting the CD47/SIRPa axis have shown encouraging efficacy in clinical trials. Meanwhile, studies on small-molecule inhibitors that interfere with CD47/SIRPa interaction or regulate CD47 expression are also in full swing. In this review, we summarize the small-molecule inhibitors interrupting the binding of CD47/SIRPa and regulating CD47 at the transcriptional, translational, and post-translational modification (PTM) levels. We provide perspectives and strategies for targeting the CD47/SIRP alpha phagocytosis checkpoint.

Automated summary

Immunotherapy is crucial in cancer treatment, with the CD47/SIRPa axis being a key focus for potential therapies. Studies on small-molecule inhibitors targeting CD47/SIRPa interaction or regulating CD47 expression are rapidly advancing, offering new perspectives and strategies for the CD47/SIRP alpha phagocytosis checkpoint.