Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTY3UE6)

• DTT Name: Voltage-gated potassium channel Kv1.3 (KCNA3)
• Synonyms: Voltage-gated potassium channel subunit Kv1.3; Voltage-gated Kv1.3 K(+) channel; Voltage-gated K(+) channel Kv1.3; Potassium channel Kv1.3; KCNA3; HuKIII; HPCN3; HLK3; HGK5
• Gene Name: KCNA3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCNA3_HUMAN
• TTD ID: T76914
• Sequence:
  MDERLSLLRSPPPPSARHRAHPPQRPASSGGAHTLVNHGYAEPAAGRELPPDMTVVPGDH
  LLEPEVADGGGAPPQGGCGGGGCDRYEPLPPSLPAAGEQDCCGERVVINISGLRFETQLK
  TLCQFPETLLGDPKRRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRIRRPVNVPIDIF
  SEEIRFYQLGEEAMEKFREDEGFLREEERPLPRRDFQRQVWLLFEYPESSGPARGIAIVS
  VLVILISIVIFCLETLPEFRDEKDYPASTSQDSFEAAGNSTSGSRAGASSFSDPFFVVET
  LCIIWFSFELLVRFFACPSKATFSRNIMNLIDIVAIIPYFITLGTELAERQGNGQQAMSL
  AILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAE
  ADDPTSGFSSIPDAFWWAVVTMTTVGYGDMHPVTIGGKIVGSLCAIAGVLTIALPVPVIV
  SNFNYFYHRETEGEEQSQYMHVGSCQHLSSSAEELRKARSNSTLSKSEYMVIEEGGMNHS
  AFPQTPFKTGNSTATCTTNNNPNSCVNIKKIFTDV
• Function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dalazatide	DMJ1NG4	Inclusion body myositis	4A41.2	Phase 1b/2a	[2]
Debio-0824	DMV401D	Psoriasis vulgaris	EA90	Phase 1b/2a	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
UK-78282	DMKBILF	Inflammation	1A00-CA43.1	Terminated	[3]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-Benzyl-7-chloro-4-hexyloxy-quinolinium	DMCX3N1	Discovery agent	N.A.	Investigative	[4]
2-Methoxy-N-(3-methyl-2-phenyl-butyl)-benzamide	DM31E6J	Discovery agent	N.A.	Investigative	[5]
4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromen-7-one	DMKMH5L	Discovery agent	N.A.	Investigative	[6]
5-(4-Phenylbutoxy)psoralen	DM3QFCV	Discovery agent	N.A.	Investigative	[7]
Correloid	DM5ISQK	Discovery agent	N.A.	Investigative	[8]
correolide	DMACH7K	Discovery agent	N.A.	Investigative	[9]
CP-339818	DMTJOWH	Discovery agent	N.A.	Investigative	[3]
[1-Benzyl-1H-quinolin-(4E)-ylidene]-hexyl-amine	DMH3BG5	Discovery agent	N.A.	Investigative	[4]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[10]

References

• [1] Durable Pharmacological Responses from the Peptide ShK-186, a Specific Kv1.3 Channel Inhibitor That Suppresses T Cell Mediators of Autoimmune Disease. J Pharmacol Exp Ther. 2012 September; 342(3): 642-653.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Angular methoxy-substituted furo- and pyranoquinolinones as blockers of the voltage-gated potassium channel Kv1.3. J Med Chem. 2001 Apr 12;44(8):1249-56.
• [4] Novel inhibitors of potassium ion channels on human T lymphocytes. J Med Chem. 1995 May 26;38(11):1877-83.
• [5] Benzamide derivatives as blockers of Kv1.3 ion channel. Bioorg Med Chem Lett. 2003 Mar 24;13(6):1161-4.
• [6] Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Mol Pharmacol. 2005 Nov;68(5):1254-70.
• [7] Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators. Mol Pharmacol. 2004 Jun;65(6):1364-74.
• [8] Potent Kv1.3 inhibitors from correolide-modification of the C18 position. Bioorg Med Chem Lett. 2005 Jan 17;15(2):447-51.
• [9] Identification and biochemical characterization of a novel nortriterpene inhibitor of the human lymphocyte voltage-gated potassium channel, Kv1.3. Biochemistry. 1999 Apr 20;38(16):4922-30.
• [10] Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227-34.