<abstract xmlns="http://www.w3.org/1999/xhtml">Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral processes. Hence, we characterized the effects of terfenadine on Kir2.x channels expressed in HEK-293 cells. Terfenadine inhibited Kir2.3 channels with a strikingly greater potency (<italic>IC</italic>50 = 1.06 ± 0.11 μmol L−1) compared to Kir2.1 channels (<italic>IC</italic>50 = 27.8 ± 4.8 μmol L−1). The Kir2.3(I213L) mutant, possessing a larger affinity for phosphatidylinositol 4,5-bisphosphate (PIP2) than the wild-type Kir2.3, was less sensitive to terfenadine inhibition (<italic>IC</italic>50 = 13.0 ± 2.9 μmol L−1). Additionally, the PIP2 intracellular application had largely reduced the inhibition of Kir2.1 channels by terfenadine. Our data support that Kir2.x channels are targets of terfena-dine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine.</abstract>

Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its anticancer properties. Lately, the subfamily 2 of inward rectifier potassium channels (Kir2) has been implicated in the progression of some tumoral processes. Hence, we characterized the effects of terfenadine on Kir2.x channels expressed in HEK-293 cells. Terfenadine inhibited Kir2.3 channels with a strikingly greater potency (IC50 = 1.06 ± 0.11 μmol L−1) compared to Kir2.1 channels (IC50 = 27.8 ± 4.8 μmol L−1). The Kir2.3(I213L) mutant, possessing a larger affinity for phosphatidylinositol 4,5-bisphosphate (PIP2) than the wild-type Kir2.3, was less sensitive to terfenadine inhibition (IC50 = 13.0 ± 2.9 μmol L−1). Additionally, the PIP2 intracellular application had largely reduced the inhibition of Kir2.1 channels by terfenadine. Our data support that Kir2.x channels are targets of terfena-dine by affecting their interaction with PIP2, which could be regarded as a mechanism of the antitumor properties of terfenadine.

Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels

Centro Universitario de Investigaciones Biomédicas

Departamento de Fisiología y Biofísica, Facultad de Medicina

Universidad Autónoma de San Luis Potosí

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

{"article-title":"Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels"}

Terfenadine is a second-generation H1-antihistamine that despite potentially can produce severe side effects it has recently gained attention due to its...

Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels

Published Online: Nov 04, 2020

Page range: 317 - 324

Accepted: Jun 28, 2020

DOI: https://doi.org/10.2478/acph-2021-0017

Keywords
terfenadine, inward rectifier potassium channels, phosphatidylinositol 4,5-bisphosphate, cationic amphiphilic drugs

© 2021 Mayra Delgado-Ramírez et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Inhibitory effect of terfenadine on Kir2.1 and Kir2.3 channels

Published Online: Nov 04, 2020

Page range: 317 - 324

Accepted: Jun 28, 2020

DOI: https://doi.org/10.2478/acph-2021-0017

Keywordsterfenadine, inward rectifier potassium channels, phosphatidylinositol 4,5-bisphosphate, cationic amphiphilic drugs

© 2021 Mayra Delgado-Ramírez et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
terfenadine, inward rectifier potassium channels, phosphatidylinositol 4,5-bisphosphate, cationic amphiphilic drugs