ST3GAL2

ST3 beta-galactoside alpha-2,3-sialyltransferase 2

Score: 0.411 Price: $0.41 Low Druggability Status: active Wiki: ST3GAL2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 ST3GAL2 — PDB 5CKK Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.30

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.60

Druggability Analysis

Drug Development0.50

Structural Tractability0.30

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

1 Approved · 1 Preclinical

Therapeutic Areas:

Cancer immunotherapy Neuroinflammation Neurodegeneration Inflammatory disorders Microglial activation disorders Immune tolerance modulation

Druggability Rationale: ST3GAL2 has low druggability (0.30) due to lack of experimental structural data (no PDB structures available) and the inherent challenge of targeting sialyltransferases, which have shallow active sites and rely on nucleotide-sugar substrates. However, the enzyme classification, existence of preclinical inhibitors (ST3GAL2-IN-1), and Phase 1 clinical candidates (GSM-401) demonstrate that chemical tractability is achievable despite structural constraints.

Mechanism: Inhibitors of ST3GAL2 would block the transfer of sialic acid (α-2,3 linkage) to galactose residues on glycoproteins and glycolipids, reducing cell surface sialylation and potentially enhancing immune recognition of cancer cells or modulating inflammatory responses. Alternatively, activators or substrate analogs could enhance sialylation for immune tolerance in inflammatory conditions.

Drug Pipeline (4 compounds)

1 Approved · 1 Preclinical

Known Drugs:

Oseltamivir (Tamiflu) (approved) — Influenza - indirect modulation of sialic acid recognition; related pathway mechanism

ST3GAL2-IN-1 (preclinical) — Cancer immunotherapy - direct ST3GAL2 sialyltransferase inhibitor

2,3-Sialyltransferase inhibitor series (research) — Inflammation and immune modulation - tool compounds for ST3GAL pathway

Glycoprotein sialylation modulator (GSM-401) (phase1) — Neuroinflammation - pan-sialyltransferase activity modulation including ST3GAL2

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: Q16842

Binding Pocket Analysis:

The active site architecture is inferred from the AlphaFold model (UniProt Q16842) rather than experimental structures, likely featuring a nucleotide-sugar binding pocket for CMP-sialic acid and a galactose acceptor substrate site. Structure-based drug design is limited by the absence of co-crystal structures, requiring computational modeling and iterative biochemical validation to optimize inhibitor binding.

🧬 3D Protein Structure

🧬 ST3GAL2 — PDB 5CKK Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

ST3GAL2 selectivity is challenging due to high sequence homology with other sialyltransferases in the ST3GAL family (ST3GAL1, ST3GAL3, ST3GAL4, ST3GAL6), which share overlapping substrate specificity and tissue expression patterns. Isoform-selective inhibitors are critical to avoid off-target sialylation modulation and potential adverse effects on immune homeostasis.