Target Information
Target General Infomation | |||||
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Target ID |
T38338
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Former ID |
TTDS00529
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Target Name |
Voltage-dependent N-type calcium channel
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Gene Name |
CACNA1B
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Synonyms |
BIII; Brain calcium channel III; Calcium channel, L type, alpha-1 polypeptide isoform 5; N-type Ca2+ channel; Voltage-dependent N-type calcium channel alpha-1B subunit; Voltage-gated calcium channel alpha subunit Cav2.2; CACNA1B
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Target Type |
Successful
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Disease | Cardiac failure [ICD10: I50] | ||||
High blood pressure [ICD9: 401; ICD10: I10-I16] | |||||
Migraine [ICD9: 346; ICD10: G43] | |||||
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Reperfusion injury [ICD10: I00-I99] | |||||
Traumatic brain injury [ICD9: 800.0-801.9, 803.0-804.9, 850.0-854.1; ICD10: S06] | |||||
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, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin- IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
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BioChemical Class |
Calcium channel
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Target Validation |
T38338
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UniProt ID | |||||
Sequence |
MVRFGDELGGRYGGPGGGERARGGGAGGAGGPGPGGLQPGQRVLYKQSIAQRARTMALYN
PIPVKQNCFTVNRSLFVFSEDNVVRKYAKRITEWPPFEYMILATIIANCIVLALEQHLPD GDKTPMSERLDDTEPYFIGIFCFEAGIKIIALGFVFHKGSYLRNGWNVMDFVVVLTGILA TAGTDFDLRTLRAVRVLRPLKLVSGIPSLQVVLKSIMKAMVPLLQIGLLLFFAILMFAII GLEFYMGKFHKACFPNSTDAEPVGDFPCGKEAPARLCEGDTECREYWPGPNFGITNFDNI LFAILTVFQCITMEGWTDILYNTNDAAGNTWNWLYFIPLIIIGSFFMLNLVLGVLSGEFA KERERVENRRAFLKLRRQQQIERELNGYLEWIFKAEEVMLAEEDRNAEEKSPLDVLKRAA TKKSRNDLIHAEEGEDRFADLCAVGSPFARASLKSGKTESSSYFRRKEKMFRFFIRRMVK AQSFYWVVLCVVALNTLCVAMVHYNQPRRLTTTLYFAEFVFLGLFLTEMSLKMYGLGPRS YFRSSFNCFDFGVIVGSVFEVVWAAIKPGSSFGISVLRALRLLRIFKVTKYWSSLRNLVV SLLNSMKSIISLLFLLFLFIVVFALLGMQLFGGQFNFQDETPTTNFDTFPAAILTVFQIL TGEDWNAVMYHGIESQGGVSKGMFSSFYFIVLTLFGNYTLLNVFLAIAVDNLANAQELTK DEEEMEEAANQKLALQKAKEVAEVSPMSAANISIAARQQNSAKARSVWEQRASQLRLQNL RASCEALYSEMDPEERLRFATTRHLRPDMKTHLDRPLVVELGRDGARGPVGGKARPEAAE APEGVDPPRRHHRHRDKDKTPAAGDQDRAEAPKAESGEPGAREERPRPHRSHSKEAAGPP EARSERGRGPGPEGGRRHHRRGSPEEAAEREPRRHRAHRHQDPSKECAGAKGERRARHRG GPRAGPREAESGEEPARRHRARHKAQPAHEAVEKETTEKEATEKEAEIVEADKEKELRNH QPREPHCDLETSGTVTVGPMHTLPSTCLQKVEEQPEDADNQRNVTRMGSQPPDPNTIVHI PVMLTGPLGEATVVPSGNVDLESQAEGKKEVEADDVMRSGPRPIVPYSSMFCLSPTNLLR RFCHYIVTMRYFEVVILVVIALSSIALAAEDPVRTDSPRNNALKYLDYIFTGVFTFEMVI KMIDLGLLLHPGAYFRDLWNILDFIVVSGALVAFAFSGSKGKDINTIKSLRVLRVLRPLK TIKRLPKLKAVFDCVVNSLKNVLNILIVYMLFMFIFAVIAVQLFKGKFFYCTDESKELER DCRGQYLDYEKEEVEAQPRQWKKYDFHYDNVLWALLTLFTVSTGEGWPMVLKHSVDATYE EQGPSPGYRMELSIFYVVYFVVFPFFFVNIFVALIIITFQEQGDKVMSECSLEKNERACI DFAISAKPLTRYMPQNRQSFQYKTWTFVVSPPFEYFIMAMIALNTVVLMMKFYDAPYEYE LMLKCLNIVFTSMFSMECVLKIIAFGVLNYFRDAWNVFDFVTVLGSITDILVTEIAETNN FINLSFLRLFRAARLIKLLRQGYTIRILLWTFVQSFKALPYVCLLIAMLFFIYAIIGMQV FGNIALDDDTSINRHNNFRTFLQALMLLFRSATGEAWHEIMLSCLSNQACDEQANATECG SDFAYFYFVSFIFLCSFLMLNLFVAVIMDNFEYLTRDSSILGPHHLDEFIRVWAEYDPAA CGRISYNDMFEMLKHMSPPLGLGKKCPARVAYKRLVRMNMPISNEDMTVHFTSTLMALIR TALEIKLAPAGTKQHQCDAELRKEISVVWANLPQKTLDLLVPPHKPDEMTVGKVYAALMI FDFYKQNKTTRDQMQQAPGGLSQMGPVSLFHPLKATLEQTQPAVLRGARVFLRQKSSTSL SNGGAIQNQESGIKESVSWGTQRTQDAPHEARPPLERGHSTEIPVGRSGALAVDVQMQSI TRRGPDGEPQPGLESQGRAASMPRLAAETQPVTDASPMKRSISTLAQRPRGTHLCSTTPD RPPPSQASSHHHHHRCHRRRDRKQRSLEKGPSLSADMDGAPSSAVGPGLPPGEGPTGCRR ERERRQERGRSQERRQPSSSSSEKQRFYSCDRFGGREPPKPKPSLSSHPTSPTAGQEPGP HPQGSGSVNGSPLLSTSGASTPGRGGRRQLPQTPLTPRPSITYKTANSSPIHFAGAQTSL PAFSPGRLSRGLSEHNALLQRDPLSQPLAPGSRIGSDPYLGQRLDSEASVHALPEDTLTF EEAVATNSGRSSRTSYVSSLTSQSHPLRRVPNGYHCTLGLSSGGRARHSYHHPDQDHWC |
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Drugs and Mode of Action | |||||
Drug(s) | LOMERIZINE | Drug Info | Approved | Migraine | [545070], [551871] |
Ziconotide | Drug Info | Approved | Pain | [527466], [539646] | |
Cilnidipine | Drug Info | Phase 3 | High blood pressure | [524770], [542719] | |
Ralfinamide | Drug Info | Phase 3 | Neuropathic pain | [536374] | |
CNV-2197944 | Drug Info | Phase 2 | Pain | [524280] | |
Ziconotide | Drug Info | Phase 1/2 | Traumatic brain injury | [537115], [539646] | |
CNSB-004 | Drug Info | Preclinical | Pain | [548809] | |
NMED-160 | Drug Info | Discontinued in Phase 2 | Pain | [547476] | |
PD-0204318 | Drug Info | Terminated | Pain | [547298] | |
PD-157667 | Drug Info | Terminated | Discovery agent | [546596] | |
PD-29361 | Drug Info | Terminated | Discovery agent | [546624] | |
TH-9229 | Drug Info | Terminated | Reperfusion injury | [546444] | |
Blocker | CaV2.2 blocker | Drug Info | [543870] | ||
Cilnidipine | Drug Info | [534852], [535452] | |||
CNV-2197944 | Drug Info | [550563] | |||
Conotoxin | Drug Info | [537656] | |||
N,N-dialkyl-dipeptidylamines | Drug Info | [534854] | |||
Ralfinamide | Drug Info | [536374] | |||
Ziconotide | Drug Info | [537115] | |||
Modulator | CNSB-004 | Drug Info | [530567] | ||
CPU-228 | Drug Info | [543870] | |||
NMED-160 | Drug Info | ||||
TH-9229 | Drug Info | [546445] | |||
Inhibitor | GNF-PF-3464 | Drug Info | [531262] | ||
HESPERIDINE | Drug Info | [531262] | |||
KYS-05090 | Drug Info | [529044] | |||
LOMERIZINE | Drug Info | [528552] | |||
NSC-180246 | Drug Info | [531262] | |||
NSC-87509 | Drug Info | [531262] | |||
PD-151307 | Drug Info | [525605] | |||
PD-157667 | Drug Info | [525576] | |||
PD-167341 | Drug Info | [525605] | |||
PD-29361 | Drug Info | [534799] | |||
PD-32577 | Drug Info | [525576] | |||
Blocker (channel blocker) | omega-conotoxin GVIA | Drug Info | [525847] | ||
Antagonist | PD-0204318 | Drug Info | [550906] | ||
Inhibitor (gating inhibitor) | TROX-1 | Drug Info | [530887] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | MAPK signaling pathway | ||||
Calcium signaling pathway | |||||
Synaptic vesicle cycle | |||||
Retrograde endocannabinoid signaling | |||||
Cholinergic synapse | |||||
Serotonergic synapse | |||||
GABAergic synapse | |||||
Dopaminergic synapse | |||||
Taste transduction | |||||
Type II diabetes mellitus | |||||
Morphine addiction | |||||
Nicotine addiction | |||||
PANTHER Pathway | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | ||||
Ionotropic glutamate receptor pathway | |||||
Metabotropic glutamate receptor group III pathway | |||||
Metabotropic glutamate receptor group II pathway | |||||
Thyrotropin-releasing hormone receptor signaling pathway | |||||
Endogenous cannabinoid signaling | |||||
GABA-B receptor II signaling | |||||
Reactome | Depolarization of the Presynaptic Terminal Triggers the Opening of Calcium Channels | ||||
WikiPathways | Calcium Regulation in the Cardiac Cell | ||||
Synaptic Vesicle Pathway | |||||
References | |||||
Ref 524280 | ClinicalTrials.gov (NCT01848730) Efficacy and Safety of CNV2197944 Versus Placebo in Patients With Post-herpetic Neuralgia. U.S. National Institutes of Health. | ||||
Ref 524770 | ClinicalTrials.gov (NCT02145104) Efficacy/Safety of Cilnidipine Plus Valsartan Versus Valsartan in Patients With Hypertension. U.S. National Institutes of Health. | ||||
Ref 537115 | Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84. | ||||
Ref 539646 | (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: 2536). | ||||
Ref 542719 | (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: 7767). | ||||
Ref 545070 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002033) | ||||
Ref 546444 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159) | ||||
Ref 546596 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009117) | ||||
Ref 546624 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009238) | ||||
Ref 547298 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014952) | ||||
Ref 547476 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016715) | ||||
Ref 525576 | Bioorg Med Chem Lett. 1999 Aug 16;9(16):2447-52.Synthesis and biological activity of substituted bis-(4-hydroxyphenyl)methanes as N-type calcium channel blockers. | ||||
Ref 525605 | J Med Chem. 1999 Oct 7;42(20):4239-49.Synthesis of a series of 4-benzyloxyaniline analogues as neuronal N-type calcium channel blockers with improved anticonvulsant and analgesic properties. | ||||
Ref 525847 | Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000 Nov 10;275(45):35335-44. | ||||
Ref 528552 | Bioorg Med Chem Lett. 2007 Feb 1;17(3):662-7. Epub 2006 Nov 6.Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. | ||||
Ref 529044 | Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3. Epub 2007 Sep 1.Discovery of potent T-type calcium channel blocker. | ||||
Ref 530567 | CNSB004 (Leconotide) causes antihyperalgesia without side effects when given intravenously: a comparison with ziconotide in a rat model of diabetic neuropathic pain. Pain Med. 2010 Feb;11(2):262-73. | ||||
Ref 530887 | Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker. J Pharmacol Exp Ther. 2010 Aug;334(2):545-55. | ||||
Ref 531262 | Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). | ||||
Ref 534799 | Bioorg Med Chem Lett. 1998 Sep 22;8(18):2415-8.Synthesis and structure-activity relationship of substituted 1,2,3,4-tetrahydroisoquinolines as N-type calcium channel blockers. | ||||
Ref 534852 | Pharmacology of N-type Ca2+ channels distributed in cardiovascular system (Review). Int J Mol Med. 1999 May;3(5):455-66. | ||||
Ref 534854 | N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. Bioorg Med Chem Lett. 1999 Mar 22;9(6):907-12. | ||||
Ref 535452 | N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an l-NAME/SHR model. J Hypertens. 2002 May;20(5):993-1000. | ||||
Ref 537115 | Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84. | ||||
Ref 537656 | Treatment with conotoxin, an 'N-type' calcium channel blocker, in neuronal hypoxic-ischemic injury. Brain Res. 1990 Dec 24;537(1-2):256-62. | ||||
Ref 543870 | (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: 533). | ||||
Ref 546445 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159) |
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