2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels

Research output: Contribution to journalJournal articlepeer-review

Standard

2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels. / Simó-Vicens, Rafel; Bomholtz, Sofia Hammami; Sørensen, Ulrik Svane; Bentzen, Bo Hjorth.

In: Frontiers in Pharmacology, Vol. 9, 1409, 03.12.2018.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Simó-Vicens, R, Bomholtz, SH, Sørensen, US & Bentzen, BH 2018, '2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels', Frontiers in Pharmacology, vol. 9, 1409. https://doi.org/10.3389/fphar.2018.01409

APA

Simó-Vicens, R., Bomholtz, S. H., Sørensen, U. S., & Bentzen, B. H. (2018). 2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels. Frontiers in Pharmacology, 9, [1409]. https://doi.org/10.3389/fphar.2018.01409

Vancouver

Simó-Vicens R, Bomholtz SH, Sørensen US, Bentzen BH. 2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels. Frontiers in Pharmacology. 2018 Dec 3;9. 1409. https://doi.org/10.3389/fphar.2018.01409

Author

Simó-Vicens, Rafel ; Bomholtz, Sofia Hammami ; Sørensen, Ulrik Svane ; Bentzen, Bo Hjorth. / 2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels. In: Frontiers in Pharmacology. 2018 ; Vol. 9.

Bibtex

@article{0903786abe5b43a3a274cc3103e83dad,
title = "2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels",
abstract = "A variety of polycyclic pyridines have been proposed as inhibitors of the small conductance calcium-activated potassium (SK) channel. To this group belongs 2,6-bis(2-benzimidazolyl)pyridine (BBP), a commercially and readily available small organic compound which has earlier been described in a broad range of chemical and biological uses. Here, we show how BBP can also be used as a potent and specific SK channel blocker in vitro. The potency of BBP was measured using automatic patch clamp on all three SK channel subtypes, resulting in similar IC50 of 0.4 μM. We also assessed the selectivity of BBP on a panel of calcium-activated and voltage-activated potassium channels using two-electrode voltage clamp, automatic and manual patch clamp. BBP did not have any effect on IK, Kir2.1, Kir3.1+Kir3.4, Kv1.5, Kv4.3/KCHIP2 and Kv7.1/KCNE1 currents and was 4.8-fold and 46-fold more potent on all SK channel subtypes vs. BK and hERG channels, respectively. Moreover, we were able to identify H491 as a critical amino acid for the pharmacological effect of BBP on the SK channel. From a medicinal chemistry perspective, BBP could be used as a starting point for the design of new and improved SK inhibitors.",
keywords = "Faculty of Health and Medical Sciences, small conductance calcium-activated potassium channels, BBP, SK channel, kca2 channel, 2,6-bis(2-benzimidazolyl)pyridine, polycyclic pyridine, blocker, inhibition, Inhibitor",
author = "Rafel Sim{\'o}-Vicens and Bomholtz, {Sofia Hammami} and S{\o}rensen, {Ulrik Svane} and Bentzen, {Bo Hjorth}",
year = "2018",
month = dec,
day = "3",
doi = "10.3389/fphar.2018.01409",
language = "English",
volume = "9",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - 2,6-Bis(2-Benzimidazolyl)Pyridine (BBP) Is a Potent and Selective Inhibitor of Small Conductance Calcium-Activated Potassium (SK) Channels

AU - Simó-Vicens, Rafel

AU - Bomholtz, Sofia Hammami

AU - Sørensen, Ulrik Svane

AU - Bentzen, Bo Hjorth

PY - 2018/12/3

Y1 - 2018/12/3

N2 - A variety of polycyclic pyridines have been proposed as inhibitors of the small conductance calcium-activated potassium (SK) channel. To this group belongs 2,6-bis(2-benzimidazolyl)pyridine (BBP), a commercially and readily available small organic compound which has earlier been described in a broad range of chemical and biological uses. Here, we show how BBP can also be used as a potent and specific SK channel blocker in vitro. The potency of BBP was measured using automatic patch clamp on all three SK channel subtypes, resulting in similar IC50 of 0.4 μM. We also assessed the selectivity of BBP on a panel of calcium-activated and voltage-activated potassium channels using two-electrode voltage clamp, automatic and manual patch clamp. BBP did not have any effect on IK, Kir2.1, Kir3.1+Kir3.4, Kv1.5, Kv4.3/KCHIP2 and Kv7.1/KCNE1 currents and was 4.8-fold and 46-fold more potent on all SK channel subtypes vs. BK and hERG channels, respectively. Moreover, we were able to identify H491 as a critical amino acid for the pharmacological effect of BBP on the SK channel. From a medicinal chemistry perspective, BBP could be used as a starting point for the design of new and improved SK inhibitors.

AB - A variety of polycyclic pyridines have been proposed as inhibitors of the small conductance calcium-activated potassium (SK) channel. To this group belongs 2,6-bis(2-benzimidazolyl)pyridine (BBP), a commercially and readily available small organic compound which has earlier been described in a broad range of chemical and biological uses. Here, we show how BBP can also be used as a potent and specific SK channel blocker in vitro. The potency of BBP was measured using automatic patch clamp on all three SK channel subtypes, resulting in similar IC50 of 0.4 μM. We also assessed the selectivity of BBP on a panel of calcium-activated and voltage-activated potassium channels using two-electrode voltage clamp, automatic and manual patch clamp. BBP did not have any effect on IK, Kir2.1, Kir3.1+Kir3.4, Kv1.5, Kv4.3/KCHIP2 and Kv7.1/KCNE1 currents and was 4.8-fold and 46-fold more potent on all SK channel subtypes vs. BK and hERG channels, respectively. Moreover, we were able to identify H491 as a critical amino acid for the pharmacological effect of BBP on the SK channel. From a medicinal chemistry perspective, BBP could be used as a starting point for the design of new and improved SK inhibitors.

KW - Faculty of Health and Medical Sciences

KW - small conductance calcium-activated potassium channels

KW - BBP

KW - SK channel

KW - kca2 channel

KW - 2,6-bis(2-benzimidazolyl)pyridine, polycyclic pyridine

KW - blocker

KW - inhibition

KW - Inhibitor

UR - https://www.frontiersin.org/articles/10.3389/fphar.2018.01409/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Pharmacology&id=424026

U2 - 10.3389/fphar.2018.01409

DO - 10.3389/fphar.2018.01409

M3 - Journal article

C2 - 30559671

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 1409

ER -

ID: 209469279