Target Information
Target General Infomation | |||||
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Target ID |
T54644
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Former ID |
TTDS00413
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Target Name |
Voltage-dependent T-type calcium channel subunit alpha-1H
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Gene Name |
CACNA1H
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Synonyms |
KCND3; Voltage-gated potassium channel subunit Kv4.3; CACNA1H
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Target Type |
Successful
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Disease | Angina pectoris [ICD9: 413; ICD10: I20] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Insomnia [ICD9: 307.41, 307.42, 327.0, 780.51, 780.52; ICD10: F51.0, G47.0] | |||||
Metabolic acidosis [ICD9: 276.2; ICD10: E87.2] | |||||
Migraine [ICD9: 346; ICD10: G43] | |||||
Ovarian cancer [ICD9: 183; ICD10: C56] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Unspecified [ICD code not available] | |||||
Function |
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, celldivision and cell death. The isoform alpha-1H gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neuronsand cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. .
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BioChemical Class |
Voltage-gated ion channel
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Target Validation |
T54644
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UniProt ID | |||||
Sequence |
MTEGARAADEVRVPLGAPPPGPAALVGASPESPGAPGREAERGSELGVSPSESPAAERGA
ELGADEEQRVPYPALAATVFFCLGQTTRPRSWCLRLVCNPWFEHVSMLVIMLNCVTLGMF RPCEDVECGSERCNILEAFDAFIFAFFAVEMVIKMVALGLFGQKCYLGDTWNRLDFFIVV AGMMEYSLDGHNVSLSAIRTVRVLRPLRAINRVPSMRILVTLLLDTLPMLGNVLLLCFFV FFIFGIVGVQLWAGLLRNRCFLDSAFVRNNNLTFLRPYYQTEEGEENPFICSSRRDNGMQ KCSHIPGRRELRMPCTLGWEAYTQPQAEGVGAARNACINWNQYYNVCRSGDSNPHNGAIN FDNIGYAWIAIFQVITLEGWVDIMYYVMDAHSFYNFIYFILLIIVGSFFMINLCLVVIAT QFSETKQRESQLMREQRARHLSNDSTLASFSEPGSCYEELLKYVGHIFRKVKRRSLRLYA RWQSRWRKKVDPSAVQGQGPGHRQRRAGRHTASVHHLVYHHHHHHHHHYHFSHGSPRRPG PEPGACDTRLVRAGAPPSPPSPGRGPPDAESVHSIYHADCHIEGPQERARVAHAAATAAA SLRLATGLGTMNYPTILPSGVGSGKGSTSPGPKGKWAGGPPGTGGHGPLSLNSPDPYEKI PHVVGEHGLGQAPGHLSGLSVPCPLPSPPAGTLTCELKSCPYCTRALEDPEGELSGSESG DSDGRGVYEFTQDVRHGDRWDPTRPPRATDTPGPGPGSPQRRAQQRAAPGEPGWMGRLWV TFSGKLRRIVDSKYFSRGIMMAILVNTLSMGVEYHEQPEELTNALEISNIVFTSMFALEM LLKLLACGPLGYIRNPYNIFDGIIVVISVWEIVGQADGGLSVLRTFRLLRVLKLVRFLPA LRRQLVVLVKTMDNVATFCTLLMLFIFIFSILGMHLFGCKFSLKTDTGDTVPDRKNFDSL LWAIVTVFQILTQEDWNVVLYNGMASTSSWAALYFVALMTFGNYVLFNLLVAILVEGFQA EGDANRSDTDEDKTSVHFEEDFHKLRELQTTELKMCSLAVTPNGHLEGRGSLSPPLIMCT AATPMPTPKSSPFLDAAPSLPDSRRGSSSSGDPPLGDQKPPASLRSSPCAPWGPSGAWSS RRSSWSSLGRAPSLKRRGQCGERESLLSGEGKGSTDDEAEDGRAAPGPRATPLRRAESLD PRPLRPAALPPTKCRDRDGQVVALPSDFFLRIDSHREDAAELDDDSEDSCCLRLHKVLEP YKPQWCRSREAWALYLFSPQNRFRVSCQKVITHKMFDHVVLVFIFLNCVTIALERPDIDP GSTERVFLSVSNYIFTAIFVAEMMVKVVALGLLSGEHAYLQSSWNLLDGLLVLVSLVDIV VAMASAGGAKILGVLRVLRLLRTLRPLRVISRAPGLKLVVETLISSLRPIGNIVLICCAF FIIFGILGVQLFKGKFYYCEGPDTRNISTKAQCRAAHYRWVRRKYNFDNLGQALMSLFVL SSKDGWVNIMYDGLDAVGVDQQPVQNHNPWMLLYFISFLLIVSFFVLNMFVGVVVENFHK CRQHQEAEEARRREEKRLRRLERRRRSTFPSPEAQRRPYYADYSPTRRSIHSLCTSHYLD LFITFIICVNVITMSMEHYNQPKSLDEALKYCNYVFTIVFVFEAALKLVAFGFRRFFKDR WNQLDLAIVLLSLMGITLEEIEMSAALPINPTIIRIMRVLRIARVLKLLKMATGMRALLD TVVQALPQVGNLGLLFMLLFFIYAALGVELFGRLECSEDNPCEGLSRHATFSNFGMAFLT LFRVSTGDNWNGIMKDTLRECSREDKHCLSYLPALSPVYFVTFVLVAQFVLVNVVVAVLM KHLEESNKEAREDAELDAEIELEMAQGPGSARRVDADRPPLPQESPGARDAPNLVARKVS VSRMLSLPNDSYMFRPVVPASAPHPRPLQEVEMETYGAGTPLGSVASVHSPPAESCASLQ IPLAVSSPARSGEPLHALSPRGTARSPSLSRLLCRQEAVHTDSLEGKIDSPRDTLDPAEP GEKTPVRPVTQGGSLQSPPRSPRPASVRTRKHTFGQRCVSSRPAAPGGEEAEASDPADEE VSHITSSACPWQPTAEPHGPEASPVAGGERDLRRLYSVDAQGFLDKPGRADEQWRPSAEL GSGEPGEAKAWGPEAEPALGARRKKKMSPPCISVEPPAEDEGSARPSAAEGGSTTLRRRT PSCEATPHRDSLEPTEGSGAGGDPAAKGERWGQASCRAEHLTVPSFAFEPLDLGVPSGDP FLDGSHSVTPESRASSSGAIVPLEPPESEPPMPVGDPPEKRRGLYLTVPQCPLEKPGSPS ATPAPGGGADDPV |
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Drugs and Mode of Action | |||||
Drug(s) | Flunarizine | Drug Info | Approved | Migraine | [538455] |
Sodium bicarbonate | Drug Info | Approved | Metabolic acidosis | [467748], [538505], [551871] | |
ABT-639 | Drug Info | Phase 2 | Pain | [533259], [542694] | |
TTA-A8 | Drug Info | Preclinical | Insomnia | [542695], [546748] | |
Mibefradil | Drug Info | Withdrawn from market | Ovarian cancer | [539642], [544589] | |
U-92032 | Drug Info | Terminated | Discovery agent | [545700] | |
Modulator | ABT-639 | Drug Info | [533259] | ||
Z 944 | Drug Info | ||||
Inhibitor | Cis-N,5-dibenzyl-6-oxomorpholine-3-carboxamide | Drug Info | [528344] | ||
GNF-PF-1967 | Drug Info | [528504] | |||
GNF-PF-4599 | Drug Info | [528504] | |||
KYS-05001 | Drug Info | [527099] | |||
KYS-05040 | Drug Info | [527099] | |||
KYS-05041 | Drug Info | [527099] | |||
KYS-05042 | Drug Info | [527099] | |||
KYS-05050 | Drug Info | [528495] | |||
KYS-05077 | Drug Info | [528495] | |||
KYS-05080 | Drug Info | [528495] | |||
Mibefradil | Drug Info | [525870] | |||
TTL-1177 | Drug Info | [543872] | |||
U-92032 | Drug Info | [525864] | |||
Blocker | DP-3005 | Drug Info | [543872] | ||
Flunarizine | Drug Info | [535918], [537585] | |||
HYP-10 | Drug Info | [543872] | |||
Sodium bicarbonate | Drug Info | [537336] | |||
Antagonist | KST-5468 | Drug Info | [543872] | ||
TTA-A8 | Drug Info | [532802] | |||
Blocker (channel blocker) | ML218 | Drug Info | [531818] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Calcium signaling pathway | |||||
Circadian entrainment | |||||
PathWhiz Pathway | Muscle/Heart Contraction | ||||
Reactome | NCAM1 interactions | ||||
WikiPathways | Corticotropin-releasing hormone | ||||
NCAM signaling for neurite out-growth | |||||
References | |||||
Ref 467748 | (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: 4507). | ||||
Ref 533259 | Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83. | ||||
Ref 538455 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 012102. | ||||
Ref 538505 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018509. | ||||
Ref 539642 | (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: 2522). | ||||
Ref 542694 | (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: 7721). | ||||
Ref 542695 | (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: 7724). | ||||
Ref 544589 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000236) | ||||
Ref 545700 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004258) | ||||
Ref 525864 | J Med Chem. 2000 Sep 7;43(18):3372-6.Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a dual Na(+) and Ca(2+) channel blocker with antioxidant activity. | ||||
Ref 525870 | Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8. | ||||
Ref 527099 | Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. | ||||
Ref 528344 | Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8. Epub 2006 Jul 28.Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. | ||||
Ref 528495 | Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5. Epub 2006 Oct 12.Synthesis and biological evaluation of novel T-type calcium channel blockers. | ||||
Ref 528504 | Bioorg Med Chem. 2007 Jan 15;15(2):1091-105. Epub 2006 Oct 30.3D pharmacophore based virtual screening of T-type calcium channel blockers. | ||||
Ref 531818 | The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742. | ||||
Ref 532802 | Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents. ACS Med Chem Lett. 2010 Aug 24;1(9):504-9. | ||||
Ref 533259 | Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83. | ||||
Ref 535918 | Migraine prophylaxis with calcium antagonists: a haemodynamic study using transcranial Doppler ultrasound. Rev Neurol. 2004 Feb 16-29;38(4):316-9. |
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