Selectivity at ligand targets
Key to terms and symbols		Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference amyloid β Hs Antibody Binding 8.7 pKd - 5,18 ⤷ pKd 8.7 (Kd 2x10-9 M) [5,18] Description: Apparent equilibrium dissociation constant determined by SPR, with immobilized Aβ42 protofibril

Targets where the ligand is described in the comment field
Target	Comment
triggering receptor expressed on myeloid cells 2	TREM2 is a membrane-bound receptor that contains an immunoglobulin V-set domain. It appears to function as a lipid-sensing receptor, with ligands including cyclophilin A [7], amyloid-β protein 42 [21,23], lipoprotein particles and apolipoproteins [21], and phospholipids [12]. Via interaction with TYROBP (TYROBP; DAP12) and spleen tyrosine kinase (SYK) phosphorylation, TREM2 regulates microglial survival, plasticity, migration and expression of inflammatory cytokines. Rare coding variants are associated with neurodegeneration in Alzheimer's disease [4,17,20]. The protein is an active target for the development of therapeutics for various neurodegenerative diseases [1-3,14,20,22]. VGL101 (iluzanebart), DNL919, and AL002 are agonistic TREM2-targeting monoclonal antibodies that are (or were) in clinical development for neurodegenerative diseases [9-10,13], although these are subject to limited brain permeability. This latter approach was proposed to activate TREM2-mediated microglial removal of amyloid β (Aβ) from the brain. In the phase 2 AL002 study changes resembling amyloid-related imaging abnormalities (ARIA) similar to those observed with the approved anti-Aβ monoclonals (aducanumab and lecanemab for example) were detected [10].