Target Information
Target General Infomation | |||||
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Target ID |
T17569
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Former ID |
TTDC00303
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Target Name |
Potassium voltage-gated channel subfamily A member 5
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Gene Name |
KCNA5
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Synonyms |
02-Sensitive Potassium Channel Kv1.5; HK2; HPCN1; Potassium channel Kv1.5; Voltage-gatedpotassium channel subunit Kv1.5; KCNA5
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Target Type |
Successful
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Disease | Atrial fibrillation [ICD9: 272, 427.31; ICD10: E78, I48] | ||||
Angina pectoris [ICD9: 413; ICD10: I20] | |||||
Arrhythmia [ICD9: 427; ICD10: I47-I49] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Function |
Voltage-gatedpotassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8505626, PubMed:12130714). May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation (PubMed:11524461).
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BioChemical Class |
Voltage-gated ion channel
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Target Validation |
T17569
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UniProt ID | |||||
Sequence |
MEIALVPLENGGAMTVRGGDEARAGCGQATGGELQCPPTAGLSDGPKEPAPKGRGAQRDA
DSGVRPLPPLPDPGVRPLPPLPEELPRPRRPPPEDEEEEGDPGLGTVEDQALGTASLHHQ RVHINISGLRFETQLGTLAQFPNTLLGDPAKRLRYFDPLRNEYFFDRNRPSFDGILYYYQ SGGRLRRPVNVSLDVFADEIRFYQLGDEAMERFREDEGFIKEEEKPLPRNEFQRQVWLIF EYPESSGSARAIAIVSVLVILISIITFCLETLPEFRDERELLRHPPAPHQPPAPAPGANG SGVMAPPSGPTVAPLLPRTLADPFFIVETTCVIWFTFELLVRFFACPSKAGFSRNIMNII DVVAIFPYFITLGTELAEQQPGGGGGGQNGQQAMSLAILRVIRLVRVFRIFKLSRHSKGL QILGKTLQASMRELGLLIFFLFIGVILFSSAVYFAEADNQGTHFSSIPDAFWWAVVTMTT VGYGDMRPITVGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETDHEEPAVLKEEQG TQSQGPGLDRGVQRKVSGSRGSFCKAGGTLENADSARRGSCPLEKCNVKAKSNVDLRRSL YALCLDTSRETDL |
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Drugs and Mode of Action | |||||
Drug(s) | Dronedarone | Drug Info | Approved | Angina pectoris | [542490], [551871] |
BMS-919373 | Drug Info | Phase 2 | Atrial fibrillation | [524787] | |
BMS-394136 | Drug Info | Phase 1 | Arrhythmia | [521687] | |
IQB-9302 | Drug Info | Phase 1 | Pain | [525954] | |
XEN-D0101 | Drug Info | Phase 1 | Atrial fibrillation | [547643] | |
XEN-D0103 | Drug Info | Phase 1 | Atrial fibrillation | [525123] | |
Dronedarone | Drug Info | Withdrawn from market | Atrial fibrillation | [536095], [542490] | |
Zatebradine | Drug Info | Terminated | Angina pectoris | [539496], [544650] | |
Inhibitor | 2-amino-2-phenyl-1,1-di(pyridin-3-yl)ethanol | Drug Info | [530800] | ||
2-morpholino-1,1,2-triphenylethanol | Drug Info | [530800] | |||
2-morpholino-1,1-di(pyridin-3-yl)hexan-1-ol | Drug Info | [530800] | |||
2-morpholino-1,1-di(pyridin-3-yl)octan-1-ol | Drug Info | [530800] | |||
2-morpholino-2-phenyl-1,1-di(pyridin-3-yl)ethanol | Drug Info | [530800] | |||
2-phenoxy-1-(2-p-tolylthiazolidin-3-yl)ethanone | Drug Info | [528519] | |||
2-phenyl-1,1-di(pyridin-3-yl)ethanol | Drug Info | [530800] | |||
3-(4-methoxybenzyloxy)-2-phenylthiazolidin-4-one | Drug Info | [528519] | |||
3-(benzyloxy)-2-(4-chlorophenyl)thiazolidin-4-one | Drug Info | [528519] | |||
3-methyl-2-morpholino-1,1-diphenylbutan-1-ol | Drug Info | [530800] | |||
4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromen-7-one | Drug Info | [531235] | |||
BMS-919373 | Drug Info | [549345] | |||
N-Benzyl-2-(toluene-4-sulfonylamino)-benzamide | Drug Info | [527067] | |||
N-Phenethyl-2-(toluene-4-sulfonylamino)-benzamide | Drug Info | [527067] | |||
XEN-D0103 | Drug Info | [543876] | |||
Modulator | BMS-394136 | Drug Info | [1572591] | ||
XEN-D0101 | Drug Info | [532208] | |||
Zatebradine | Drug Info | ||||
Blocker (channel blocker) | clofilium | Drug Info | [533766] | ||
tetraethylammonium | Drug Info | [533612] | |||
Antagonist | DPO-1 | Drug Info | [543876] | ||
Blocker | Dronedarone | Drug Info | [536095] | ||
NIP-142 | Drug Info | [536095] | |||
RS-100302 | Drug Info | [536095] | |||
S-20951 | Drug Info | [536095] | |||
S-9947 | Drug Info | [536095] | |||
Opener | IQB-9302 | Drug Info | [525954] | ||
XEN-D0104 | Drug Info | [543876] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
PathWhiz Pathway | Muscle/Heart Contraction | ||||
Reactome | Voltage gated Potassium channels | ||||
WikiPathways | Potassium Channels | ||||
References | |||||
Ref 521687 | ClinicalTrials.gov (NCT00162448) A Phase I Study to Assess the Electrophysiologic Effects of BMS-394136 on the Atrium and Ventricle in Patients With Dual-Chamber Pacemakers or Defibrillators. U.S. National Institutes of Health. | ||||
Ref 524787 | ClinicalTrials.gov (NCT02156076) A Blinded Study to Evaluate Effect on Atrial Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation. U.S. National Institutes of Health. | ||||
Ref 525123 | ClinicalTrials.gov (NCT02390258) Fed-Fasted, Single and Multiple Ascending Dose Trial of XEN-D0103. U.S. National Institutes of Health. | ||||
Ref 525954 | Stereoselective effects of the enantiomers of a new local anaesthetic, IQB-9302, on a human cardiac potassium channel (Kv1.5). Br J Pharmacol. 2001 Jan;132(2):385-92. | ||||
Ref 536095 | New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22. | ||||
Ref 539496 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2358). | ||||
Ref 542490 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7465). | ||||
Ref 544650 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000429) | ||||
Ref 525954 | Stereoselective effects of the enantiomers of a new local anaesthetic, IQB-9302, on a human cardiac potassium channel (Kv1.5). Br J Pharmacol. 2001 Jan;132(2):385-92. | ||||
Ref 527067 | Bioorg Med Chem Lett. 2004 Jun 7;14(11):2823-7.Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel. | ||||
Ref 528519 | Bioorg Med Chem Lett. 2007 Jan 1;17(1):282-4. Epub 2006 Nov 13.Evolution of thiazolidine-based blockers of human Kv1.5 for the treatment of atrial arrhythmias. | ||||
Ref 530800 | Bioorg Med Chem Lett. 2010 Apr 15;20(8):2493-6. Epub 2010 Mar 4.Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel. | ||||
Ref 531235 | Bioorg Med Chem Lett. 2010 Dec 1;20(23):6989-92. Epub 2010 Oct 23.Substituted N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs as potent Kv1.3 ion channel blockers. Part 2. | ||||
Ref 532208 | Human electrophysiological and pharmacological properties of XEN-D0101: a novel atrial-selective Kv1.5/IKur inhibitor. J Cardiovasc Pharmacol. 2013 May;61(5):408-15. | ||||
Ref 533612 | 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. | ||||
Ref 533766 | Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel. Mol Pharmacol. 1995 Jan;47(1):198-205. | ||||
Ref 536095 | New antiarrhythmic agents for atrial fibrillation and atrial flutter. Expert Opin Emerg Drugs. 2005 May;10(2):311-22. | ||||
Ref 543876 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 542). |
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