CHR2

Channelrhodopsin-2

Score: 0.546 Price: $0.55 Low Druggability Status: active Wiki: CHR2

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🔮 CHR2 — AlphaFold A0FGR8 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.33

Clinical Stage

Phase II

Target Class

Ion Channel

Safety

0.80

Druggability Analysis

Drug Development0.30

Structural Tractability0.30

Target Class0.85

Safety Profile0.80

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Retinitis pigmentosa and inherited retinal dystrophies Age-related macular degeneration (AMD) Vision restoration in photoreceptor degeneration Neuromodulation and optogenetic therapeutics Spinal cord injury and neural circuit repair

Druggability Rationale: CHR2 presents moderate druggability (0.55 score) primarily as a gene therapy target rather than through traditional small-molecule or biologics approaches. While the ion channel architecture and light-gated mechanism are well-characterized, the lack of PDB crystal structures and reliance on AlphaFold predictions limit rational drug design, though the investigational status of channelrhodopsin activators demonstrates feasibility of pharmacological modulation.

Mechanism: CHR2 functions as a light-gated cation channel that opens in response to blue light (470nm), allowing depolarization through Na+ and Ca2+ influx. Therapeutic approaches would involve delivering CHR2 via gene therapy to degenerated neurons or photoreceptors, enabling light-dependent control of neural activity for vision restoration or neuromodulation applications.

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

Channelrhodopsin-2 activators (investigational) — Optogenetic tool, blue light activation

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: A0FGR8

Binding Pocket Analysis:

The light-gated mechanism centers on a retinal chromophore binding pocket within the transmembrane helical bundle, characteristic of microbial opsins; structural insights derive primarily from AlphaFold modeling (resolution equivalent ~2.1Å) rather than experimental crystallography. The ion selectivity filter and gating mechanism involve conserved residues in the pore-forming region, representing potential sites for pharmacological enhancement or modulation of channel kinetics.

Selectivity & Safety Considerations

Selectivity is less critical than for traditional ion channels since CHR2 is typically delivered via gene therapy to specific cell populations; however, cross-reactivity with endogenous channelrhodopsin orthologs or off-target light-sensitive proteins must be evaluated. Tissue-specific promoters and delivery vectors provide inherent selectivity advantages over systemic small-molecule approaches.