TREM-2 Agonist

AL002 is a humanized monoclonal IgG1 antibody and a blood-brain barrier-permeable TREM2 modulator. AL002 binds to TREM2 on the surface of microglia, promotes TREM2 clustering and the formation of the TREM2-DAP12 complex, activates the TREM2 signaling pathway and PI3K cascade, and induces TREM2 internalization and degradation. AL002 is applicable to research related to Alzheimer's disease.

TREM2 agonist-5 is the microglial lipid-sensing receptor (TREM2) agonist with a K_d of 71.36 μM. TREM2 agonist-5 is a racemic structural analog of the TREM2 agonist VG-3927 and exhibits superior microglial phagocytosis and activates TREM2 signaling in HEK293-hTREM2/DAP12 cells. TREM2 agonist-5 displays a superior in vitro pharmacokinetic profile to VG-3927. TREM2 agonist-5 can used for the study of Alzheimer’s disease.

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.

DNL-919 ATV is a brain-penetrant TREM2 agonist. DNL-919 ATV induces responsive microglial cell state changes and modulates microglial biomarkers. DNL-919 ATV can be used for the research of Alzheimer's disease.

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.

DNL-919 (TAK-920) is a human IgG1 monoclonal antibody (mAb) targeting TREM-2. DNL-919 can be used in Alzheimer's disease research. Recommended isotype control: Human IgG1 kappa, Isotype Control (HY-P99001).