Syk Activator

As48 is a selective TREM2 agonist with a K_D value of 12.48 μM in TRIC binding assay. As48 binds near the TREM2 cleavage region, forms hydrogen bonds with Gly68, reduces conformational flexibility in regions 58-102, restricts protease accessibility to the cleavage site. As48 activates SYK phosphorylation, enhances microglial phagocytosis, and induces downstream calcium signaling in TREM2-expressing cells. As48 inhibits TREM2 ectodomain shedding without affecting ADAM10/17 protease activities. As48 can be used for the research of Alzheimer's disease.

TREM2 agonist-3 (Compound 4i) is a TREM2 agonist with a K_D value of 19.0 µM. The K_D value of TREM2 agonist-3 for TREM1 is 39.8 µM. TREM2 agonist-3 induces an increase in phosphorylated SYK levels. TREM2 agonist-3 can be used in the research of neurodegenerative diseases and other diseases associated with TREM2 dysfunction.

VHB937 is a potent and selective TREM2 agonist, a human monoclonal antibody, with sub-nanomolar affinity. VHB937 enhances TREM2 surface expression and downstream signaling, such as Syk phosphorylation and calcium mobilization. VHB937 exhibits robust neuroprotective effects in vivo, significantly reducing pathology and pro-inflammatory markers across a broad range of animal models of neuroinflammation and neurodegeneration. VHB937 can be used for neurodegenerative diseases research.

T2M-010 is a potent, brain-penetrant TREM2 agonist (K_d = 0.83 μM). T2M-010 activates receptor-proximal signaling, inducing SYK phosphorylation in TREM2-expressing cells, and promotes microglial phagocytosis. T2M-010 can be used for the study of protective microglial responses relevant to Alzheimer’s disease (AD).