General Information of Drug Therapeutic Target (DTT) (ID: TTZPWGN)

DTT Name Voltage-gated calcium channel alpha Cav3.2 (CACNA1H)
Synonyms Voltage-gated calcium channel subunit alpha Cav3.2; Voltage-dependent T-type calcium channel subunit alpha-1H; Low-voltage-activated calcium channel alpha1 3.2 subunit
Gene Name CACNA1H
DTT Type
Successful target
[1]
BioChemical Class
Voltage-gated ion channel
UniProt ID
CAC1H_HUMAN
TTD ID
T54644
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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
Function
Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probable). They may also be involved in the modulation of firing patterns of neurons. In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
Calcium signaling pathway (hsa04020 )
Circadian entrainment (hsa04713 )
Reactome Pathway
NCAM1 interactions (R-HSA-419037 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Flunarizine DMZU5JP Migraine 8A80 Approved [2]
Sodium bicarbonate DMMU6BJ Metabolic acidosis 5C73 Approved [1]
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2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ABT-639 DMEWQ4X Pain MG30-MG3Z Phase 2 [3]
Mibefradil DMU9VDS Glioblastoma multiforme 2A00.0 Phase 1 [4]
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1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
TTA-A8 DMWZCIF Insomnia 7A00-7A0Z Preclinical [5]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
U-92032 DMTYO3P N. A. N. A. Terminated [6]
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16 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cis-N,5-dibenzyl-6-oxomorpholine-3-carboxamide DM75SO4 Discovery agent N.A. Investigative [7]
DP-3005 DMXEVA2 Angina pectoris BA40 Investigative [8]
GNF-PF-1967 DMGSRLA Discovery agent N.A. Investigative [9]
GNF-PF-4599 DM1ZMUN Discovery agent N.A. Investigative [9]
HYP-10 DMW9HTL Pain MG30-MG3Z Investigative [8]
KST-5468 DMT0CR5 Pain MG30-MG3Z Investigative [8]
KYS-05001 DM3MID9 Discovery agent N.A. Investigative [10]
KYS-05040 DM1JU8F Discovery agent N.A. Investigative [10]
KYS-05041 DMVA6LH Discovery agent N.A. Investigative [10]
KYS-05042 DMM6G4H Discovery agent N.A. Investigative [10]
KYS-05050 DMXR3V4 Solid tumour/cancer 2A00-2F9Z Investigative [11]
KYS-05077 DMHW40F Discovery agent N.A. Investigative [11]
KYS-05080 DM57BXZ Discovery agent N.A. Investigative [11]
ML218 DM3D21X Discovery agent N.A. Investigative [12]
TTL-1177 DMDM7C6 Solid tumour/cancer 2A00-2F9Z Investigative [8]
Z 944 DMFT51X Discovery agent N.A. Investigative [13]
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⏷ Show the Full List of 16 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Ovarian cancer 2C82 Ovarian tissue 1.31E-04 -0.76 -2.12
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The Drug Transporter (DTP) Role of This DTT

DTT DTP Name Voltage-gated calcium channel alpha Cav3.2 (CACNA1H) DTP Info
Gene Name CACNA1H

References

1 Acute renal failure. Clin Evid (Online). 2008 Sep 3;2008. pii: 2001.
2 Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys. 2009;55(2):81-93.
3 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.
4 Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8.
5 Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents. ACS Med Chem Lett. 2010 Aug 24;1(9):504-9.
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 ... J Med Chem. 2000 Sep 7;43(18):3372-6.
7 Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8.
8 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: 536).
9 3D pharmacophore based virtual screening of T-type calcium channel blockers. Bioorg Med Chem. 2007 Jan 15;15(2):1091-105.
10 3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
11 Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
12 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.
13 Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.PLoS One.2015 Aug 14;10(8):e0130012.