Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPXI3S)

• DTT Name: Voltage-gated potassium channel Kv7.2 (KCNQ2)
• Synonyms: Voltage-gated potassium channel subunit Kv7.2; Neuroblastoma-specific potassium channel alpha subunit KvLQT2; Neuroblastoma-specific potassium channel KQT-like 2; KQT-like 2; KCNQ2; K+ channel KCNQ2
• Gene Name: KCNQ2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCNQ2_HUMAN
• TTD ID: T74483
• Sequence:
  MVQKSRNGGVYPGPSGEKKLKVGFVGLDPGAPDSTRDGALLIAGSEAPKRGSILSKPRAG
  GAGAGKPPKRNAFYRKLQNFLYNVLERPRGWAFIYHAYVFLLVFSCLVLSVFSTIKEYEK
  SSEGALYILEIVTIVVFGVEYFVRIWAAGCCCRYRGWRGRLKFARKPFCVIDIMVLIASI
  AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLLGSVVYAHSKELVTAWYIGF
  LCLILASFLVYLAEKGENDHFDTYADALWWGLITLTTIGYGDKYPQTWNGRLLAATFTLI
  GVSFFALPAGILGSGFALKVQEQHRQKHFEKRRNPAAGLIQSAWRFYATNLSRTDLHSTW
  QYYERTVTVPMYSSQTQTYGASRLIPPLNQLELLRNLKSKSGLAFRKDPPPEPSPSKGSP
  CRGPLCGCCPGRSSQKVSLKDRVFSSPRGVAAKGKGSPQAQTVRRSPSADQSLEDSPSKV
  PKSWSFGDRSRARQAFRIKGAASRQNSEEASLPGEDIVDDKSCPCEFVTEDLTPGLKVSI
  RAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAGHLDMLSRIKSLQSRVDQIVGRGPAIT
  DKDRTKGPAEAELPEDPSMMGRLGKVEKQVLSMEKKLDFLVNIYMQRMGIPPTETEAYFG
  AKEPEPAPPYHSPEDSREHVDRHGCIVKIVRSSSSTGQKNFSAPPAAPPVQCPPSTSWQP
  QSHPRQGHGTSPVGDHGSLVRIPPPPAHERSLSAYGGGNRASMEFLRQEDTPGCRPPEGN
  LRDSDTSISIPSVDHEELERSFSGFSISQSKENLDALNSCYAAVAPCAKVRPYIAEGESD
  TDSDLCTPCGPPPRSATGEGPFGDVGWAGPRK
• Function: Probably importantin the regulation of neuronal excitability. Associates with kcnq3 to form a potassium channel with essentially identical properties to the channel underlying the native m-current.
• KEGG Pathway: Cholinergic synapse (hsa04725)
• Reactome Pathway:
  Interaction between L1 and Ankyrins (R-HSA-445095)
  Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DTT

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ICA-69673	DM1RZVI	Pain	MG30-MG3Z	Preclinical	[1]

9 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]
ICA-27243	DMO0N3Q	Discovery agent	N.A.	Investigative	[3]
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[4]
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[5]
QO-58	DMYXPF8	Discovery agent	N.A.	Investigative	[6]
XE991	DMLH1PK	Discovery agent	N.A.	Investigative	[7]
zinc pyrithione	DMF0CRA	Discovery agent	N.A.	Investigative	[8]
ztz240	DM60N3C	Discovery agent	N.A.	Investigative	[9]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[10]

References

• [1] Voltage-gated Potassium Channels as Therapeutic Drug Targets
• [2] The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77.
• [3] The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site. Neurosci Lett. 2009 Nov 13;465(2):138-42.
• [4] Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2447-52.
• [5] Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005 Oct 26;25(43):9825-35.
• [6] Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1,5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol. 2013 Feb;168(4):1030-42.
• [7] KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998 Dec 4;282(5395):1890-3.
• [8] Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96.
• [9] Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions. J Biol Chem. 2010 Sep 3;285(36):28322-32.
• [10] Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol. 2000 Sep;58(3):591-600.