A Medicinal Chemistry Perspective on Protein Tyrosine Phosphatase Nonreceptor Type 2 in Tumor Immunology

PTPN2 (protein tyrosine phosphatase nonreceptor type 2) is an important member of the protein tyrosine phosphatase (PTP) family. It plays a crucial role in dephosphorylating tyrosine-phosphorylated proteins and modulating critical signaling pathways associated with T-cell receptors, IL-2, IFNγ, and various cytokines. In recent years, the PTPN2's biological role has been clarified, particularly since its association with tumor immunology was gradually revealed in 2017, making it a star target for cancer immunotherapy. The dual inhibitor AC484, which targets both PTPN2 and PTP1B, is currently undergoing phase I clinical trials. This advancement has attracted great interest from researchers to develop new drugs based on its unique structure. This review outlines the structural modification processes of PTPN2-targeted agents, focusing primarily on inhibitors and degraders. Finally, this review endeavors to provide a comprehensive perspective on the evolving field of PTPN2-targeted drug discovery for tumor immunotherapy, offering valuable insights for future drug development.