TREM2

Triggering receptor expressed on myeloid cells 2

Score: 0.628 Price: $0.63 Low Druggability Status: active Wiki: TREM2

🔴 Alzheimer's Disease 🔥 Neuroinflammation 🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

1533

DEBATES

3D Protein Structure

🧬 TREM2 — PDB 5UD7 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.42

Clinical Stage

Phase II

Target Class

Receptor

Safety

0.60

Druggability Analysis

Drug Development0.30

Structural Tractability0.85

Target Class0.70

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

3 Preclinical

Druggability Rationale: TREM2 demonstrates medium druggability (0.55) due to its well-characterized extracellular immunoglobulin domain amenable to antibody targeting, supported by 12 available PDB structures at high resolution (1.47 Å). The validated biological mechanism (loss-of-function mutations in AD) and advanced clinical candidates (AL002 in Phase II) confirm target tractability, though the medium score reflects challenges in achieving optimal microglial activation without immunological complications.

Mechanism: Agonist antibodies that enhance TREM2 signaling to promote microglial function

Drug Pipeline (4 compounds)

3 Preclinical

Known Drugs:

AL002 (latozinemab) (Phase II) — Anti-TREM2 agonist antibody for AD (Alector/AbbVie)

AL044 (preclinical) — Anti-TREM2 antibody, enhanced microglial phagocytosis

DNL919 (preclinical) — Brain-penetrant TREM2 agonist (Denali)

4D9 antibody (preclinical) — TREM2 agonist antibody, enhances microglial function

Structural Data:

PDB (12) ✓AlphaFold ✓Cryo-EM —

5ELI 5UD7 5UD8 6B8O 6XDS+7 more

UniProt: Q9NZC2

🧬 3D Protein Structure

🧬 TREM2 — PDB 5UD7 Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

TREM2 selectivity is relatively favorable as it is primarily expressed on myeloid cells (microglia, macrophages, dendritic cells) with restricted CNS distribution, minimizing off-target peripheral immune activation. However, antibody-based agonists must carefully avoid Fcγ receptor cross-linking that could trigger unintended immune responses or neurotoxic cytokine release.