PTPRS

PTPRS (Receptor-type tyrosine-protein phosphatase S), also known as PTPσ or SAP-1, is a transmembrane protein tyrosine phosphatase regulating cellular communication through extracellular domain-mediated interactions. It modulates neuronal development by balancing tyrosine phosphorylation of synaptic adhesion molecules and guidance receptors, while influencing immune cell activation via T-cell receptor signaling crosstalk. Its dual roles in neuroimmune interfaces link it to neurodegenerative disorders like multiple sclerosis and Alzheimer's disease, as well as malignancies including glioblastoma and hormone-resistant breast cancers.
Drug discovery targeting PTPRS focuses on extracellular domain-blocking biologics. A monoclonal antibody (VAX-014) has demonstrated enhanced neural regeneration in spinal injury models by disrupting inhibitory phosphatase-substrate interactions. Small-molecule allosteric inhibitors, such as compound 10d, show promise in suppressing autoimmune arthritis in preclinical studies. However, challenges remain in achieving isoform specificity due to structural homology within the PTPR family. No clinical-stage candidates have been reported as of 2023.