Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIVDM3)

• DTT Name: Voltage-gated potassium channel Kv7.3 (KCNQ3)
• Synonyms: Voltage-gated potassium channel subunit Kv7.3; Potassium channel alpha subunit KvLQT3; Potassium channel KQT-like 3; KQT-like 3; KCNQ3; K+ channel KCNQ3
• Gene Name: KCNQ3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCNQ3_HUMAN
• TTD ID: T54132
• Sequence:
  MGLKARRAAGAAGGGGDGGGGGGGAANPAGGDAAAAGDEERKVGLAPGDVEQVTLALGAG
  ADKDGTLLLEGGGRDEGQRRTPQGIGLLAKTPLSRPVKRNNAKYRRIQTLIYDALERPRG
  WALLYHALVFLIVLGCLILAVLTTFKEYETVSGDWLLLLETFAIFIFGAEFALRIWAAGC
  CCRYKGWRGRLKFARKPLCMLDIFVLIASVPVVAVGNQGNVLATSLRSLRFLQILRMLRM
  DRRGGTWKLLGSAICAHSKELITAWYIGFLTLILSSFLVYLVEKDVPEVDAQGEEMKEEF
  ETYADALWWGLITLATIGYGDKTPKTWEGRLIAATFSLIGVSFFALPAGILGSGLALKVQ
  EQHRQKHFEKRRKPAAELIQAAWRYYATNPNRIDLVATWRFYESVVSFPFFRKEQLEAAS
  SQKLGLLDRVRLSNPRGSNTKGKLFTPLNVDAIEESPSKEPKPVGLNNKERFRTAFRMKA
  YAFWQSSEDAGTGDPMAEDRGYGNDFPIEDMIPTLKAAIRAVRILQFRLYKKKFKETLRP
  YDVKDVIEQYSAGHLDMLSRIKYLQTRIDMIFTPGPPSTPKHKKSQKGSAFTFPSQQSPR
  NEPYVARPSTSEIEDQSMMGKFVKVERQVQDMGKKLDFLVDMHMQHMERLQVQVTEYYPT
  KGTSSPAEAEKKEDNRYSDLKTIICNYSETGPPEPPYSFHQVTIDKVSPYGFFAHDPVNL
  PRGGPSSGKVQATPPSSATTYVERPTVLPILTLLDSRVSCHSQADLQGPYSDRISPRQRR
  SITRDSDTPLSLMSVNHEELERSPSGFSISQDRDDYVFGPNGGSSWMREKRYLAEGETDT
  DTDPFTPSGSMPLSSTGDGISDSVWTPSNKPI
• Function: Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs.
• 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 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Retigabine	DMGNYIH	Behcet disease	4A62	Approved	[2]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Linopirdine	DM0ZOGX	Cognitive impairment	6D71	Phase 3	[1]
ICA-105665	DMP925B	Epilepsy	8A60-8A68	Phase 2	[3]
XEN1101	DMJVL57	Epilepsy	8A60-8A68	Phase 1	[4]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ICA-69673	DM1RZVI	Pain	MG30-MG3Z	Preclinical	[5]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-32577	DMBA15J	Discovery agent	N.A.	Investigative	[6]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[7]

References

• [1] The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1. J Pharmacol Sci. 2010;114(3):332-40.
• [2] The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels. Epilepsia. 2012 Apr;53(4):606-12.
• [3] New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Curr Neurol Neurosci Rep. 2008 Jul;8(4):345-52.
• [4] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [5] Voltage-gated Potassium Channels as Therapeutic Drug Targets
• [6] 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.
• [7] Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br J Pharmacol. 2000 Feb;129(3):413-5.