As48

As48 is a selective TREM2 agonist with a KD value of 12.48 μM in the TRIC binding assay. It binds near the TREM2 cleavage region, forming a hydrogen bond with Gly68, which reduces conformational flexibility in the 58-102 region and limits protease access to the cleavage site. As48 activates SYK phosphorylation, enhances microglial phagocytosis, and induces downstream calcium signaling pathways in cells expressing TREM2. It inhibits the shedding of the TREM2 ectodomain without affecting the protease activity of ADAM10/17. As48 is used in Alzheimer's disease research.