Summary of probe development for inhibitors of the two-pore domain potassium channel KCNK9
Name: Primary cell-based screen for identification of compounds that inhibit the two-pore domain potassium channel KCNK9 ..more
Sequence: potassium channel subfamily K member 9 [Homo sapiens]
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Depositor Specified Assays
Name: Primary cell-based screen for identification of compounds that inhibit the two-pore domain potassium channel KCNK9
Data Source: Johns Hopkins Ion Channel Center (JHICC_KCNK9_Inh_Summary)
BioAssay Type: Summary
Depositor Category: NIH Molecular Libraries Probe Production Network
Source (MLPCN Center Name): Johns Hopkins Ion Channel Center (JHICC)
Center Affiliation: Johns Hopkins University, School of Medicine
Screening Center PI: Min Li, Ph.D.
Assay Provider: Meng Wu, Ph.D. , Johns Hopkins University, School of Medicine
Network: Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1 R03 MH090849-01
Grant Proposal PI: Meng Wu, Ph.D. , Johns Hopkins University, School of Medicine
Assay Implementation: Melissa Miller, Joseph Babcock, Amy Scott M.S., Shunyou Long M.S., David Meyers Ph.D., Owen McManus Ph.D., and Meng Wu Ph.D.
KCNK9 (also termed K2p9.1 or TASK-3) is a member of the two-pore domain family (KCNK) of potassium channels that contribute to resting membrane potential and the regulation of cell excitability by generating background currents [1-2].
In addition to its role in neurons where KCNK9 is most abundantly expressed, recent studies show that KCNK9 plays critical roles in a wide variety of human pathophysiologies. For example, KCNK9 is overexpressed in various human cancers and its exogenous overexpression promotes cell proliferation in culture and tumor development in animal models [3-4]. Moreover, KCNK9 deficiency causes a primary hyperaldosteronism in mouse . A more recent study reports that KCNK9 mutation causes Birk Barel mental retardation dysmorphism syndrome in humans . These findings suggest that KCNK9 may be a potential new therapeutic target for treating human diseases . However, there are no suitable chemical probes to investigate the physiological roles of KCNK9 channels.
The objective of the current screen is to identify compounds that inhibit the flow of ions through KCNK9 using a HEK293 cell line that stably expresses this channel. Compounds selected as KCNK9 inhibitors will later be counter-screened for specificity.
KCNK9, TASK3, Two-pore domain potassium channel 9, HTS assay, 384, primary, inhibitor, blocker, FDSS, Thallium, fluorescence, Kinetic, FluxOR, JHICC, Johns Hopkins, Molecular Libraries Probe Production Centers Network, MLPCN.
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