PLIN2

Perilipin 2

Score: 0.505 Price: $0.50 Undruggable Druggability Status: active Wiki: PLIN2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

292

DEBATES

3D Protein Structure

🧬 PLIN2 — PDB 5LLX Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Undruggable

Score: 0.23

Clinical Stage

Approved

Target Class

Structural Protein

Safety

0.60

Druggability Analysis

Drug Development0.80

Structural Tractability0.30

Target Class0.50

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

1 Approved · 2 Preclinical

Druggability Rationale: PLIN2 presents low druggability due to its structural protein classification lacking typical deep binding pockets required for small-molecule inhibitors, compounded by the absence of crystal structures (PDB unavailable, 0 structures) that would facilitate rational drug design. However, precedent exists through indirect modulators (thiazolidinediones) and lipase inhibitors (GSK2163511, atglistatin) that alter PLIN2 function via upstream pathway modulation rather than direct binding, suggesting alternative drugging strategies beyond orthosteric inhibition.

Mechanism: Direct PLIN2 inhibitors would reduce lipid droplet formation and stability, promoting lipid mobilization and reducing pathological lipid accumulation. Indirect approaches target upstream regulators of PLIN2 expression or modulate associated lipases to alter lipid storage dynamics in metabolic and neurodegenerative disease states.

Drug Pipeline (4 compounds)

1 Approved · 2 Preclinical

Known Drugs:

Atglistatin (preclinical) — Lipid metabolism disorder; research tool for adipose triglyceride lipase inhibition

A-922500 (preclinical) — Obesity and metabolic dysfunction; adipose triglyceride lipase inhibitor

GSK2163511 (phase1) — Non-alcoholic fatty liver disease (NAFLD); adipose triglyceride lipase inhibitor affecting lipid droplet dynamics

Thiazolidinediones (pioglitazone, rosiglitazone) (approved) — Type 2 diabetes; indirect modulation of lipid droplet proteins and lipid metabolism pathways

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: Q5SYF3

🧬 3D Protein Structure

🧬 PLIN2 — PDB 5LLX Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

PLIN2 is one of five perilipin family members (PLIN1-5) with overlapping lipid droplet localization and function, creating significant selectivity challenges for direct inhibitors. Off-target engagement with PLIN1, PLIN3, or associated lipases (ATGL, HSL) could confound therapeutic efficacy and safety, necessitating structure-guided approaches or isoform-selective allosteric modulators.