VU0810464, a non‐urea G protein‐gated inwardly rectifying K+ (Kir3/GIRK) channel activator, exhibits enhanced selectivity for neuronal Kir3 channels and reduces stress‐induced hyperthermia in mice

G protein‐gated inwardly rectifying K+ (Kir3) channels moderate the activity of excitable cells and have been implicated in neurological disorders and cardiac arrhythmias. Most neuronal Kir3 channels consist of Kir3.1 and Kir3.2 subtypes, while cardiac Kir3 channels consist of Kir3.1 and Kir3.4 subtypes. Previously, we identified a family of urea‐containing Kir3 channel activators, but these molecules exhibit suboptimal pharmacokinetic properties and modest selectivity for Kir3.1/3.2 relative to Kir3.1/3.4 channels. Here, we characterize a non‐urea activator, VU0810464, which displays nanomolar potency as a Kir3.1/3.2 activator, improved selectivity for neuronal Kir3 channels, and improved brain penetration.

• Publication year

  2019

• Venue

  British Journal of Pharmacology

• Publication date

  2019-07-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1111/bph.14671PMID 30924523PMCID PMC6555862
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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