Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8HGRW)

DTT Name Voltage-gated potassium channel Kv7.4 (KCNQ4)
Synonyms Voltage-gated potassium channel subunit Kv7.4; Potassium channel alpha subunit KvLQT4; KQT-like 4; KCNQ4
Gene Name KCNQ4
DTT Type
Literature-reported target
 [1]
BioChemical Class
Voltage-gated ion channel
UniProt ID
KCNQ4_HUMAN
TTD ID
T55916
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAEAPPRRLGLGPPPGDAPRAELVALTAVQSEQGEAGGGGSPRRLGLLGSPLPPGAPLPG
PGSGSGSACGQRSSAAHKRYRRLQNWVYNVLERPRGWAFVYHVFIFLLVFSCLVLSVLST
IQEHQELANECLLILEFVMIVVFGLEYIVRVWSAGCCCRYRGWQGRFRFARKPFCVIDFI
VFVASVAVIAAGTQGNIFATSALRSMRFLQILRMVRMDRRGGTWKLLGSVVYAHSKELIT
AWYIGFLVLIFASFLVYLAEKDANSDFSSYADSLWWGTITLTTIGYGDKTPHTWLGRVLA
AGFALLGISFFALPAGILGSGFALKVQEQHRQKHFEKRRMPAANLIQAAWRLYSTDMSRA
YLTATWYYYDSILPSFRELALLFEHVQRARNGGLRPLEVRRAPVPDGAPSRYPPVATCHR
PGSTSFCPGESSRMGIKDRIRMGSSQRRTGPSKQHLAPPTMPTSPSSEQVGEATSPTKVQ
KSWSFNDRTRFRASLRLKPRTSAEDAPSEEVAEEKSYQCELTVDDIMPAVKTVIRSIRIL
KFLVAKRKFKETLRPYDVKDVIEQYSAGHLDMLGRIKSLQTRVDQIVGRGPGDRKAREKG
DKGPSDAEVVDEISMMGRVVKVEKQVQSIEHKLDLLLGFYSRCLRSGTSASLGAVQVPLF
DPDITSDYHSPVDHEDISVSAQTLSISRSVSTNMD
Function
Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1muscarinic receptors.
KEGG Pathway
Cholinergic synapse (hsa04725 )
Reactome Pathway
Voltage gated Potassium channels (R-HSA-1296072 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
7 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide DMGFOQJ Discovery agent N.A. Investigative [2]
ML213 DMFAUGP Discovery agent N.A. Investigative [3]
NC00075159 DMJCYMW Discovery agent N.A. Investigative [1]
PIP2 DMOZV7N Discovery agent N.A. Investigative [4]
XE991 DMLH1PK Discovery agent N.A. Investigative [5]
zinc pyrithione DMF0CRA Discovery agent N.A. Investigative [6]
[14C]TEA DM6SFYH Discovery agent N.A. Investigative [7]
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⏷ Show the Full List of 7 Investigative Drug(s)

References

1 Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay. Anal Biochem. 2011 Nov 1;418(1):66-72.
2 The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77.
3 Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011 Oct 19;2(10):572-577.
4 Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005 Oct 26;25(43):9825-35.
5 KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Am J Physiol Cell Physiol. 2001 Apr;280(4):C859-66.
6 Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96.
7 Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem. 2008 Nov 7;283(45):30668-76.