ArticleActa pharmacologica Sinica2013
Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels.
Article in Acta pharmacologica Sinica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 16 citations in OpenAlex.
- ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.Acta pharmacologica Sinica · 2022Article
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity.ACS medicinal chemistry letters · 2019Article
- Targeted Treatment in Childhood Epilepsy Syndromes.Current treatment options in neurology · 2016Review
- Advancing epilepsy genetics in the genomic era.Genome medicine · 2015Review
- The protease inhibitor atazanavir blocks hERG K(+) channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane.Acta pharmacologica Sinica · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimRetigabine, an activator of KCNQ2-5 channels, is currently used to treat partial-onset seizures. The aim of this study was to explore the possibility that structure modification of retigabine could lead to novel inhibitors of KCNQ2 channels, which were valuable tools for KCNQ channel studies.
methodsA series of retigabine derivatives was designed and synthesized. KCNQ2 channels were expressed in CHO cells. KCNQ2 currents were recorded using whole-cell voltage clamp technique. Test compound in extracellular solution was delivered to the recorded cell using an ALA 8 Channel Solution Exchange System.
resultsA total of 23 retigabine derivatives (HN31-HN410) were synthesized and tested electrophysiologically. Among the compounds, HN38 was the most potent inhibitor of KCNQ2 channels (its IC50 value=0.10 ± 0.05 μmol/L), and was 7-fold more potent than the classical KCNQ inhibitor XE991. Further analysis revealed that HN38 (3 μmol/L) had no detectable effect on channel activation, but accelerated deactivation at hyperpolarizing voltages. In contrast, XE991 (3 μmol/L) did not affect the kinetics of channel activation and deactivation.
conclusionThe retigabine derivative HN38 is a potent KCNQ2 inhibitor, which differs from XE991 in its influence on the channel kinetics. Our study provides a new strategy for the design and development of potent KCNQ2 channel inhibitors.
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