Target Information
Target General Information | Top | |||||
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Target ID |
T51115
(Former ID: TTDS00414)
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Target Name |
Voltage-gated calcium channel alpha Cav1.2 (CACNA1C)
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Synonyms |
Voltage-gated calcium channel subunit alpha Cav1.2; Voltage-dependent L-type calcium channel subunit alpha-1C; Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle; CCHL1A1; CACNL1A1; CACN2; CACH2
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Gene Name |
CACNA1C
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Alzheimer disease [ICD-11: 8A20] | |||||
Function |
Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
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BioChemical Class |
Voltage-gated ion channel
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UniProt ID | ||||||
Sequence |
MVNENTRMYIPEENHQGSNYGSPRPAHANMNANAAAGLAPEHIPTPGAALSWQAAIDAAR
QAKLMGSAGNATISTVSSTQRKRQQYGKPKKQGSTTATRPPRALLCLTLKNPIRRACISI VEWKPFEIIILLTIFANCVALAIYIPFPEDDSNATNSNLERVEYLFLIIFTVEAFLKVIA YGLLFHPNAYLRNGWNLLDFIIVVVGLFSAILEQATKADGANALGGKGAGFDVKALRAFR VLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFMGKMHKTCYN QEGIADVPAEDDPSPCALETGHGRQCQNGTVCKPGWDGPKHGITNFDNFAFAMLTVFQCI TMEGWTDVLYWVNDAVGRDWPWIYFVTLIIIGSFFVLNLVLGVLSGEFSKEREKAKARGD FQKLREKQQLEEDLKGYLDWITQAEDIDPENEDEGMDEEKPRNMSMPTSETESVNTENVA GGDIEGENCGARLAHRISKSKFSRYWRRWNRFCRRKCRAAVKSNVFYWLVIFLVFLNTLT IASEHYNQPNWLTEVQDTANKALLALFTAEMLLKMYSLGLQAYFVSLFNRFDCFVVCGGI LETILVETKIMSPLGISVLRCVRLLRIFKITRYWNSLSNLVASLLNSVRSIASLLLLLFL FIIIFSLLGMQLFGGKFNFDEMQTRRSTFDNFPQSLLTVFQILTGEDWNSVMYDGIMAYG GPSFPGMLVCIYFIILFICGNYILLNVFLAIAVDNLADAESLTSAQKEEEEEKERKKLAR TASPEKKQELVEKPAVGESKEEKIELKSITADGESPPATKINMDDLQPNENEDKSPYPNP ETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEASAFFIFSSNNRFRLQCHRIVNDT IFTNLILFFILLSSISLAAEDPVQHTSFRNHILFYFDIVFTTIFTIEIALKILGNADYVF TSIFTLEIILKMTAYGAFLHKGSFCRNYFNILDLLVVSVSLISFGIQSSAINVVKILRVL RVLRPLRAINRAKGLKHVVQCVFVAIRTIGNIVIVTTLLQFMFACIGVQLFKGKLYTCSD SSKQTEAECKGNYITYKDGEVDHPIIQPRSWENSKFDFDNVLAAMMALFTVSTFEGWPEL LYRSIDSHTEDKGPIYNYRVEISIFFIIYIIIIAFFMMNIFVGFVIVTFQEQGEQEYKNC ELDKNQRQCVEYALKARPLRRYIPKNQHQYKVWYVVNSTYFEYLMFVLILLNTICLAMQH YGQSCLFKIAMNILNMLFTGLFTVEMILKLIAFKPKGYFSDPWNVFDFLIVIGSIIDVIL SETNHYFCDAWNTFDALIVVGSIVDIAITEVNPAEHTQCSPSMNAEENSRISITFFRLFR VMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLIVMLFFIYAVIGMQVFGKIALNDTTE INRNNNFQTFPQAVLLLFRCATGEAWQDIMLACMPGKKCAPESEPSNSTEGETPCGSSFA VFYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWAEYDPEAKGRI KHLDVVTLLRRIQPPLGFGKLCPHRVACKRLVSMNMPLNSDGTVMFNATLFALVRTALRI KTEGNLEQANEELRAIIKKIWKRTSMKLLDQVVPPAGDDEVTVGKFYATFLIQEYFRKFK KRKEQGLVGKPSQRNALSLQAGLRTLHDIGPEIRRAISGDLTAEEELDKAMKEAVSAASE DDIFRRAGGLFGNHVSYYQSDGRSAFPQTFTTQRPLHINKAGSSQGDTESPSHEKLVDST FTPSSYSSTGSNANINNANNTALGRLPRPAGYPSTVSTVEGHGPPLSPAIRVQEVAWKLS SNRERHVPMCEDLELRRDSGSAGTQAHCLLLRKANPSRCHSRESQAAMAGQEETSQDETY EVKMNHDTEACSEPSLLSTEMLSYQDDENRQLTLPEEDKRDIRQSPKRGFLRSASLGRRA SFHLECLKRQKDRGGDISQKTVLPLHLVHHQALAVAGLSPLLQRSHSPASFPRPFATPPA TPGSRGWPPQPVPTLRLEGVESSEKLNSSFPSIHCGSWAETTPGGGGSSAARRVRPVSLM VPSQAGAPGRQFHGSASSLVEAVLISEGLGQFAQDPKFIEVTTQELADACDMTIEEMESA ADNILSGGAPQSPNGALLPFVNCRDAGQDRAGGEEDAGCVRARGRPSEEELQDSRVYVSS L Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T77YFO |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | RAUWOLFIA SERPENTINA ROOT | Drug Info | Approved | Discovery agent | [1] | |
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ARC029 | Drug Info | Phase 3 | Alzheimer disease | [2] | |
Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
1 | R-56865 | Drug Info | Terminated | Angina pectoris | [3] | |
2 | SNAP-5089 | Drug Info | Terminated | Heart arrhythmia | [4], [5] | |
3 | TH-9229 | Drug Info | Terminated | Reperfusion injury | [6] | |
Mode of Action | [+] 5 Modes of Action | + | ||||
Inhibitor | [+] 10 Inhibitor drugs | + | ||||
1 | RAUWOLFIA SERPENTINA ROOT | Drug Info | [1] | |||
2 | ARC029 | Drug Info | [7] | |||
3 | CGS-27830 | Drug Info | [8] | |||
4 | NIGULDIPINE | Drug Info | [1] | |||
5 | R-56865 | Drug Info | [9] | |||
6 | SNAP-5089 | Drug Info | [10] | |||
7 | CORYNANTHEINE | Drug Info | [1] | |||
8 | CV-4093 | Drug Info | [7] | |||
9 | MEBUDIPINE | Drug Info | [15] | |||
10 | PD-32577 | Drug Info | [16] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | TH-9229 | Drug Info | [11] | |||
2 | CPU-228 | Drug Info | [13] | |||
Blocker (channel blocker) | [+] 1 Blocker (channel blocker) drugs | + | ||||
1 | (-)-(R)-efonidipine | Drug Info | [12] | |||
Activator | [+] 3 Activator drugs | + | ||||
1 | (-)-(S)-BayK8644 | Drug Info | [13] | |||
2 | FPL64176 | Drug Info | [14] | |||
3 | SZ(+)-(S)-202-791 | Drug Info | [13] | |||
Inhibitor (gating inhibitor) | [+] 3 Inhibitor (gating inhibitor) drugs | + | ||||
1 | [3H](+)-cis-diltiazem | Drug Info | [17] | |||
2 | [3H](+)-isradipine | Drug Info | [18] | |||
3 | [3H](-)devapamil | Drug Info | [19] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. J Med Chem. 1995 Sep 15;38(19):3681-716. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031727) | |||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000253) | |||||
REF 4 | URL: 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: 498). | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006771) | |||||
REF 6 | 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 7 | Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity. J Med Chem. 1989 Oct;32(10):2399-406. | |||||
REF 8 | CGS 27830, a potent nonpeptide endothelin receptor antagonist, Bioorg. Med. Chem. Lett. 3(10):2099-2104 (1993). | |||||
REF 9 | Novel calcium antagonists with both calcium overload inhibition and antioxidant activity. 1. 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-(aminopropyl)... J Med Chem. 1998 Oct 22;41(22):4309-16. | |||||
REF 10 | Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8. | |||||
REF 11 | 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 12 | Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels. Br J Pharmacol. 2004 Dec;143(8):1050-7. | |||||
REF 13 | URL: 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: 529). | |||||
REF 14 | The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents. Neuropharmacology. 2003 Aug;45(2):281-92. | |||||
REF 15 | Antagonism of 4-substituted 1,4-dihydropyridine-3,5-dicarboxylates toward voltage-dependent L-type Ca2+ channels Ca V 1.3 and Ca V 1.2. Bioorg Med Chem. 2010 May 1;18(9):3147-58. | |||||
REF 16 | 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. | |||||
REF 17 | SR 33557, a novel calcium entry blocker. II. Interactions with 1,4-dihydropyridine, phenylalkylamine and benzothiazepine binding sites in rat heart sarcolemmal membranes. J Pharmacol Exp Ther. 1990 Nov;255(2):600-7. | |||||
REF 18 | Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest. 2004 May;113(10):1430-9. | |||||
REF 19 | Pharmacological, radioligand binding, and electrophysiological characteristics of FPL 64176, a novel nondihydropyridine Ca2+ channel activator, in cardiac and vascular preparations. Mol Pharmacol. 1991 Nov;40(5):734-41. |
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