Target Information
Target General Information | Top | |||||
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Target ID |
T24793
(Former ID: TTDR00620)
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Target Name |
Voltage-gated calcium channel alpha Cav1.3 (CACNA1D)
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Synonyms |
Voltage-gated calcium channel alpha subunit Cav1.3; Voltage-gated L-type Ca2+ channel alpha1D; Calcium channel, L type, alpha-1 polypeptide, isoform 2; CACNA1D
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Gene Name |
CACNA1D
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Alzheimer disease [ICD-11: 8A20] | |||||
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-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
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BioChemical Class |
Voltage-gated ion channel
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UniProt ID | ||||||
Sequence |
MMMMMMMKKMQHQRQQQADHANEANYARGTRLPLSGEGPTSQPNSSKQTVLSWQAAIDAA
RQAKAAQTMSTSAPPPVGSLSQRKRQQYAKSKKQGNSSNSRPARALFCLSLNNPIRRACI SIVEWKPFDIFILLAIFANCVALAIYIPFPEDDSNSTNHNLEKVEYAFLIIFTVETFLKI IAYGLLLHPNAYVRNGWNLLDFVIVIVGLFSVILEQLTKETEGGNHSSGKSGGFDVKALR AFRVLRPLRLVSGVPSLQVVLNSIIKAMVPLLHIALLVLFVIIIYAIIGLELFIGKMHKT CFFADSDIVAEEDPAPCAFSGNGRQCTANGTECRSGWVGPNGGITNFDNFAFAMLTVFQC ITMEGWTDVLYWMNDAMGFELPWVYFVSLVIFGSFFVLNLVLGVLSGEFSKEREKAKARG DFQKLREKQQLEEDLKGYLDWITQAEDIDPENEEEGGEEGKRNTSMPTSETESVNTENVS GEGENRGCCGSLCQAISKSKLSRRWRRWNRFNRRRCRAAVKSVTFYWLVIVLVFLNTLTI SSEHYNQPDWLTQIQDIANKVLLALFTCEMLVKMYSLGLQAYFVSLFNRFDCFVVCGGIT ETILVELEIMSPLGISVFRCVRLLRIFKVTRHWTSLSNLVASLLNSMKSIASLLLLLFLF IIIFSLLGMQLFGGKFNFDETQTKRSTFDNFPQALLTVFQILTGEDWNAVMYDGIMAYGG PSSSGMIVCIYFIILFICGNYILLNVFLAIAVDNLADAESLNTAQKEEAEEKERKKIARK ESLENKKNNKPEVNQIANSDNKVTIDDYREEDEDKDPYPPCDVPVGEEEEEEEEDEPEVP AGPRPRRISELNMKEKIAPIPEGSAFFILSKTNPIRVGCHKLINHHIFTNLILVFIMLSS AALAAEDPIRSHSFRNTILGYFDYAFTAIFTVEILLKMTTFGAFLHKGAFCRNYFNLLDM LVVGVSLVSFGIQSSAISVVKILRVLRVLRPLRAINRAKGLKHVVQCVFVAIRTIGNIMI VTTLLQFMFACIGVQLFKGKFYRCTDEAKSNPEECRGLFILYKDGDVDSPVVRERIWQNS DFNFDNVLSAMMALFTVSTFEGWPALLYKAIDSNGENIGPIYNHRVEISIFFIIYIIIVA FFMMNIFVGFVIVTFQEQGEKEYKNCELDKNQRQCVEYALKARPLRRYIPKNPYQYKFWY VVNSSPFEYMMFVLIMLNTLCLAMQHYEQSKMFNDAMDILNMVFTGVFTVEMVLKVIAFK PKGYFSDAWNTFDSLIVIGSIIDVALSEADPTESENVPVPTATPGNSEESNRISITFFRL FRVMRLVKLLSRGEGIRTLLWTFIKSFQALPYVALLIAMLFFIYAVIGMQMFGKVAMRDN NQINRNNNFQTFPQAVLLLFRCATGEAWQEIMLACLPGKLCDPESDYNPGEEYTCGSNFA IVYFISFYMLCAFLIINLFVAVIMDNFDYLTRDWSILGPHHLDEFKRIWSEYDPEAKGRI KHLDVVTLLRRIQPPLGFGKLCPHRVACKRLVAMNMPLNSDGTVMFNATLFALVRTALKI KTEGNLEQANEELRAVIKKIWKKTSMKLLDQVVPPAGDDEVTVGKFYATFLIQDYFRKFK KRKEQGLVGKYPAKNTTIALQAGLRTLHDIGPEIRRAISCDLQDDEPEETKREEEDDVFK RNGALLGNHVNHVNSDRRDSLQQTNTTHRPLHVQRPSIPPASDTEKPLFPPAGNSVCHNH HNHNSIGKQVPTSTNANLNNANMSKAAHGKRPSIGNLEHVSENGHHSSHKHDREPQRRSS VKRTRYYETYIRSDSGDEQLPTICREDPEIHGYFRDPHCLGEQEYFSSEECYEDDSSPTW SRQNYGYYSRYPGRNIDSERPRGYHHPQGFLEDDDSPVCYDSRRSPRRRLLPPTPASHRR SSFNFECLRRQSSQEEVPSSPIFPHRTALPLHLMQQQIMAVAGLDSSKAQKYSPSHSTRS WATPPATPPYRDWTPCYTPLIQVEQSEALDQVNGSLPSLHRSSWYTDEPDISYRTFTPAS LTVPSSFRNKNSDKQRSADSLVEAVLISEGLGRYARDPKFVSATKHEIADACDLTIDEME SAASTLLNGNVRPRANGDVGPLSHRQDYELQDFGPGYSDEEPDPGRDEEDLADEMICITT L Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ARC029 | Drug Info | Phase 3 | Alzheimer disease | [2] | |
Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
1 | SIPATRIGINE | Drug Info | Discontinued in Phase 2 | Neurological disorder | [3] | |
2 | SNAP-5089 | Drug Info | Terminated | Heart arrhythmia | [4], [5] | |
3 | TH-9229 | Drug Info | Terminated | Reperfusion injury | [6] | |
Mode of Action | [+] 4 Modes of Action | + | ||||
Inhibitor | [+] 8 Inhibitor drugs | + | ||||
1 | ARC029 | Drug Info | [1] | |||
2 | SIPATRIGINE | Drug Info | [7] | |||
3 | CGS-27830 | Drug Info | [8] | |||
4 | SNAP-5089 | Drug Info | [9] | |||
5 | CV-4093 | Drug Info | [1] | |||
6 | MEBUDIPINE | Drug Info | [13] | |||
7 | N,N'-Di-acenaphthen-5-yl-guanidine | Drug Info | [7] | |||
8 | PD-32577 | Drug Info | [14] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | TH-9229 | Drug Info | [10] | |||
2 | CPU-228 | Drug Info | [11] | |||
Activator | [+] 1 Activator drugs | + | ||||
1 | (-)-(S)-BayK8644 | Drug Info | [11] | |||
Inhibitor (gating inhibitor) | [+] 2 Inhibitor (gating inhibitor) drugs | + | ||||
1 | azidopine | Drug Info | [12] | |||
2 | [3H](+)-isradipine | Drug Info | [15] |
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-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Dihydropyrimidines: novel calcium antagonists with potent and long-lasting vasodilative and antihypertensive activity. J Med Chem. 1989 Oct;32(10):2399-406. | |||||
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 800003904) | |||||
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 | Synthesis and characterization of N-(acenaphth-5-yl)-N'-(4-methoxynaphth-1-yl)guanidine as a glutamate release inhibitor and potential anti-ischemic agent, Bioorg. Med. Chem. Lett. 5(19):2259-2262 (1995). | |||||
REF 8 | CGS 27830, a potent nonpeptide endothelin receptor antagonist, Bioorg. Med. Chem. Lett. 3(10):2099-2104 (1993). | |||||
REF 9 | Discovery of alpha 1a-adrenergic receptor antagonists based on the L-type Ca2+ channel antagonist niguldipine. J Med Chem. 1995 May 12;38(10):1579-81. | |||||
REF 10 | 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 11 | 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: 530). | |||||
REF 12 | Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. | |||||
REF 13 | 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 14 | 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 15 | alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J Biol Chem. 2001 Jun 22;276(25):22100-6. |
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