CERS2

Ceramide synthase 2

Score: 0.508 Price: $0.51 Low Druggability Status: active Wiki: CERS2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 CERS2 — PDB 5YSR Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.28

Clinical Stage

Phase II

Target Class

Enzyme

Safety

0.40

Druggability Analysis

Drug Development0.30

Structural Tractability0.30

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

Druggability Rationale: CERS2 has low druggability (0.30) despite being an enzyme with an established active site, primarily due to the lack of available crystal structures (0 PDB entries) and the mycotoxin nature of the only known inhibitor (Fumonisin B1), which raises safety concerns for clinical translation. However, the AlphaFold model availability and validation in Phase 2 clinical trials suggest that structure-based drug design approaches may still yield selective, non-toxic inhibitors with improved pharmacological properties.

Mechanism: CERS2 inhibitors would reduce the enzymatic synthesis of very long-chain ceramides by blocking the condensation of serine and palmitoyl-CoA, thereby decreasing ceramide-mediated neuroinflammation and apoptosis implicated in neurodegenerative pathology. This modulation of the ceramide signaling cascade may provide neuroprotective effects in Alzheimer's disease and related neurodegenerative conditions.

Drug Pipeline (1 compounds)

Known Drugs:

Fumonisin B1 (research) — Ceramide synthase inhibitor (tool compound, mycotoxin)

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: H0YNU7

🧬 3D Protein Structure

🧬 CERS2 — PDB 5YSR Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

CERS2 selectivity against other ceramide synthase isoforms (CERS1, CERS3–CERS6) is critical, as off-target inhibition could disrupt ceramide homeostasis and cause unintended lipid metabolism alterations in non-neuronal tissues. The substrate specificity for very long-chain (C22–C26) fatty acids may provide a degree of isoform selectivity, but comprehensive kinetic profiling will be essential.