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LAG-3 inhibitors and ligands target lymphocyte activation gene-3 (LAG-3), an inhibitory receptor on T cells. The gene was cloned in 1990 from activated lymphocytes, and its protein is closely related to the coreceptor cluster of differentiation 4 (CD4). Like CD4, LAG-3 binds major histocompatibility complex class II (MHC-II) molecules on antigen-presenting cells. A 2019 study identified fibrinogen-like protein 1 (FGL1), a liver-secreted protein, as a further major inhibitory ligand. LAG-3 is often coexpressed with programmed cell death protein 1 (PD-1) on exhausted T cells. Ieramilimab is an anti-LAG-3 antibody, and SA-15-P is a small molecule reported to block both the LAG-3/MHC-II and LAG-3/FGL1 interactions. LAG-3-IN-2 and LAG-3 degrader 1 extend the small-molecule tools for this checkpoint receptor.
LAG-3 degrader 1 is a PROTAC target protein ligand designed for the synthesis of PROTACs targeting LAG-3. This compound facilitates the targeted degradation of LAG-3, demonstrating significant anti-tumor activity. It serves as a valuable tool in cancer research, allowing for the exploration of LAG-3 modulation in therapeutic applications.
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