RELN

Reelin

Score: 0.483 Price: $0.48 Low Druggability Status: active Wiki: RELN

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

106

DEBATES

3D Protein Structure

🧬 RELN — PDB 5ES4 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.33

Clinical Stage

Approved

Target Class

Signaling Protein

Safety

0.50

Druggability Analysis

Drug Development0.60

Structural Tractability0.70

Target Class0.50

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

2 Preclinical

Druggability Rationale: The druggability of RELN for neurodegeneration appears challenging due to its complex signaling mechanism and limited direct small molecule targeting options. While preclinical research suggests potential therapeutic approaches through receptor agonists (VLDLR/ApoER2) or downstream pathway modulators, the lack of high-resolution structural data and clinically validated interventions currently constrains direct pharmaceutical development. The most promising near-term strategies likely involve recombinant protein approaches or indirect signaling cascade enhancements rather than traditional small molecule inhibition/activation.

Mechanism: Drugs targeting RELN would primarily work by enhancing reelin expression or signaling through its receptors (VLDLR and ApoER2) to promote neuronal migration, synaptic plasticity, and cognitive function. Alternatively, pathway modulators could enhance downstream signaling cascades (Dab1-mediated pathways) to compensate for reelin deficiency or dysfunction.

Drug Pipeline (4 compounds)

2 Preclinical

Known Drugs:

Leptin (recombinant) (research) — Reelin pathway modulation in neurological disorders

VPS34 inhibitors (e.g., SAR405) (preclinical) — Autophagy regulation affecting reelin signaling

SorLA/LR11 modulators (research) — Reelin receptor trafficking and synaptic plasticity

VLDLR agonists (preclinical) — Reelin receptor activation for neuronal migration disorders

Structural Data:

PDB (6) ✓AlphaFold ✓Cryo-EM —

2E26 3A7Q 5B4X 6A48 7LYU+1 more

UniProt: P78509

🧬 3D Protein Structure

🧬 RELN — PDB 5ES4 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity challenges arise from RELN's broad expression in the CNS and its interaction with multiple receptors (VLDLR, ApoER2, integrin α3β1), potentially limiting isoform-specific targeting. Off-target effects may occur through modulation of related lipoprotein receptor pathways or autophagy processes when using indirect pathway modulators.