CD45 inhibitors comprise a group of compounds that are designed to specifically target and modulate the function of CD45, a protein tyrosine phosphatase that plays a key role in T-cell receptor signaling. CD45, also known as the leukocyte common antigen (LCA), is a type I transmembrane protein expressed on all nucleated cells of hematopoietic origin except erythrocytes and plasma cells. CD45 is an essential regulator of the signaling thresholds controlling immune responses, making it a scientifically interesting target. The role of CD45 in immune function is complex and nuanced. CD45 exists in multiple isoforms, generated by alternative splicing of exons 4, 5, and 6, which encode the extracellular domain of the protein. These isoforms vary in size and glycosylation state, and they have differential expression patterns on various cell types. These isoforms can have distinct and sometimes opposing roles in signal transduction. Therefore, an understanding of the isoform-specific functions of CD45 is critical for the development of inhibitors that can selectively target specific isoforms.
Inhibitors of CD45 are typically designed to target the enzymatic activity of the protein, which resides in its cytoplasmic domain. This domain has phosphatase activity, removing phosphate groups from tyrosine residues on target proteins. Modulation of this phosphatase activity can impact the signaling pathways in which CD45 is involved, including T-cell receptor signaling and B-cell receptor signaling.