HCN1

Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1

Score: 0.574 Price: $0.57 Medium Druggability Status: active Wiki: HCN1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

127

DEBATES

3D Protein Structure

🧬 HCN1 — PDB 5U6O Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.51

Clinical Stage

Approved

Target Class

Ion Channel

Safety

0.60

Druggability Analysis

Drug Development0.75

Structural Tractability0.85

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Druggability Rationale: HCN1 represents a moderately promising neurodegeneration drug target, with its ion channel blocking potential demonstrating potential therapeutic utility, particularly given its known role in neuronal excitability and epilepsy-related pathologies. The availability of structural data, including multiple PDB entries and AlphaFold predictions, provides a promising foundation for rational drug design, though the current lack of clinical trials specifically targeting this gene suggests significant translational challenges remain. The existing proof-of-concept with small molecule channel blockers like Ivabradine indicates potential druggability, but more research is needed to validate neurodegeneration-specific therapeutic approaches.

Mechanism: HCN1 encodes a hyperpolarization-activated cyclic nucleotide-gated channel critical for neuronal pacemaking and synaptic integration, with dysregulation linked to hyperexcitability disorders and potential neurodegeneration mechanisms. Specifically, HCN1 channel dysfunction can alter neuronal excitability, synaptic plasticity, and potentially contribute to neuronal death or dysfunction in conditions like epilepsy and neurodegenerative diseases.

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

Ivabradine (approved) — Heart failure, angina

Structural Data:

PDB (12) ✓AlphaFold ✓Cryo-EM ✓

3U0Z 5U6O 5U6P 6UQF 6UQG+7 more

UniProt: A0A0U1RQR7

🧬 3D Protein Structure

🧬 HCN1 — PDB 5U6O Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

HCN channel selectivity is critical due to four isoforms (HCN1-4) with distinct tissue and functional distributions; HCN1 selectivity over cardiac HCN4 is essential to avoid bradycardia and conduction abnormalities seen with Ivabradine. The neuronal predominance of HCN1 versus HCN4's cardiac enrichment provides a favorable selectivity window, though isoform cross-reactivity must be rigorously profiled in preclinical development.