HCN channels as targets for drug discovery

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Michael P Maher1, Nyan-Tsz Wu, Hong-Qing Guo

  • 1Johnson & Johnson Pharmaceutical Research and Development, L.L.C., San Diego, CA 92121, USA.

Combinatorial Chemistry & High Throughput Screening
|January 20, 2009
PubMed

Insights

Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are crucial for heart rate and neuronal activity. Blocking these channels may offer new pain relief strategies for nerve injury.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are non-selective cation channels involved in regulating heart rate and neuronal excitability.
  • HCN channels are the molecular basis for the hyperpolarization-activated current I(h).

Purpose of the Study:

  • To review evidence supporting the role of HCN channels in sensory neurons and pain sensation.
  • To summarize the development and validation of screening methods for novel HCN channel blockers.

Main Methods:

  • Literature review of molecular and pharmacological evidence.
  • Description of efforts in developing and validating screening assays for HCN channel blockers.

Main Results:

  • Emerging evidence implicates HCN channels in sensory neuron function and pain, especially in injury-related pain.
  • Methods for screening HCN channel blockers have been developed and validated.

Conclusions:

  • HCN channels are potential therapeutic targets for novel analgesic agents.
  • The developed screening methods facilitate the discovery of new pain management drugs.

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