Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTHAQIM)

DTP Name	Voltage-gated calcium channel subunit alpha Cav3.1 (CACNA1G)
Gene Name	CACNA1G
UniProt ID	O43497 (CAC1G_HUMAN)
VARIDT ID	DTD0541
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Synonyms	Cav3.1c; NBR13; Voltage-dependent T-type calcium channel subunit alpha-1G
DTP Family	Na+/K+/Ca2+ Channel Targeting Tarantula Huwentoxin (THT) Family ;
Tissue Specificity	Highly expressed in brain, in particular in the amygdala, subthalamic nuclei, cerebellum and thalamus. Moderate expression in heart; low expression in placenta, kidney and lung. Also expressed in colon and bone marrow and in tumoral cells to a lesser extent. Highly expressed in fetal brain, but also in peripheral fetal tissues as heart, kidney and lung, suggesting a developmentally regulated expression.
Sequence	MDEEEDGAGAEESGQPRSFMRLNDLSGAGGRPGPGSAEKDPGSADSEAEGLPYPALAPVV FFYLSQDSRPRSWCLRTVCNPWFERISMLVILLNCVTLGMFRPCEDIACDSQRCRILQAF DDFIFAFFAVEMVVKMVALGIFGKKCYLGDTWNRLDFFIVIAGMLEYSLDLQNVSFSAVR TVRVLRPLRAINRVPSMRILVTLLLDTLPMLGNVLLLCFFVFFIFGIVGVQLWAGLLRNR CFLPENFSLPLSVDLERYYQTENEDESPFICSQPRENGMRSCRSVPTLRGDGGGGPPCGL DYEAYNSSSNTTCVNWNQYYTNCSAGEHNPFKGAINFDNIGYAWIAIFQVITLEGWVDIM YFVMDAHSFYNFIYFILLIIVGSFFMINLCLVVIATQFSETKQRESQLMREQRVRFLSNA STLASFSEPGSCYEELLKYLVYILRKAARRLAQVSRAAGVRVGLLSSPAPLGGQETQPSS SCSRSHRRLSVHHLVHHHHHHHHHYHLGNGTLRAPRASPEIQDRDANGSRRLMLPPPSTP ALSGAPPGGAESVHSFYHADCHLEPVRCQAPPPRSPSEASGRTVGSGKVYPTVHTSPPPE TLKEKALVEVAASSGPPTLTSLNIPPGPYSSMHKLLETQSTGACQSSCKISSPCLKADSG ACGPDSCPYCARAGAGEVELADREMPDSDSEAVYEFTQDAQHSDLRDPHSRRQRSLGPDA EPSSVLAFWRLICDTFRKIVDSKYFGRGIMIAILVNTLSMGIEYHEQPEELTNALEISNI VFTSLFALEMLLKLLVYGPFGYIKNPYNIFDGVIVVISVWEIVGQQGGGLSVLRTFRLMR VLKLVRFLPALQRQLVVLMKTMDNVATFCMLLMLFIFIFSILGMHLFGCKFASERDGDTL PDRKNFDSLLWAIVTVFQILTQEDWNKVLYNGMASTSSWAALYFIALMTFGNYVLFNLLV AILVEGFQAEEISKREDASGQLSCIQLPVDSQGGDANKSESEPDFFSPSLDGDGDRKKCL ALVSLGEHPELRKSLLPPLIIHTAATPMSLPKSTSTGLGEALGPASRRTSSSGSAEPGAA HEMKSPPSARSSPHSPWSAASSWTSRRSSRNSLGRAPSLKRRSPSGERRSLLSGEGQESQ DEEESSEEERASPAGSDHRHRGSLEREAKSSFDLPDTLQVPGLHRTASGRGSASEHQDCN GKSASGRLARALRPDDPPLDGDDADDEGNLSKGERVRAWIRARLPACCLERDSWSAYIFP PQSRFRLLCHRIITHKMFDHVVLVIIFLNCITIAMERPKIDPHSAERIFLTLSNYIFTAV FLAEMTVKVVALGWCFGEQAYLRSSWNVLDGLLVLISVIDILVSMVSDSGTKILGMLRVL RLLRTLRPLRVISRAQGLKLVVETLMSSLKPIGNIVVICCAFFIIFGILGVQLFKGKFFV CQGEDTRNITNKSDCAEASYRWVRHKYNFDNLGQALMSLFVLASKDGWVDIMYDGLDAVG VDQQPIMNHNPWMLLYFISFLLIVAFFVLNMFVGVVVENFHKCRQHQEEEEARRREEKRL RRLEKKRRNLMLDDVIASGSSASAASEAQCKPYYSDYSRFRLLVHHLCTSHYLDLFITGV IGLNVVTMAMEHYQQPQILDEALKICNYIFTVIFVLESVFKLVAFGFRRFFQDRWNQLDL AIVLLSIMGITLEEIEVNASLPINPTIIRIMRVLRIARVLKLLKMAVGMRALLDTVMQAL PQVGNLGLLFMLLFFIFAALGVELFGDLECDETHPCEGLGRHATFRNFGMAFLTLFRVST GDNWNGIMKDTLRDCDQESTCYNTVISPIYFVSFVLTAQFVLVNVVIAVLMKHLEESNKE AKEEAELEAELELEMKTLSPQPHSPLGSPFLWPGVEGPDSPDSPKPGALHPAAHARSASH FSLEHPTDRQLFDTISLLIQGSLEWELKLMDELAGPGGQPSAFPSAPSLGGSDPQIPLAE MEALSLTSEIVSEPSCSLALTDDSLPDDMHTLLLSALESNMQPHPTELPGPDLLTVRKSG VSRTHSLPNDSYMCRHGSTAEGPLGHRGWGLPKAQSGSVLSVHSQPADTSYILQLPKDAP HLLQPHSAPTWGTIPKLPPPGRSPLAQRPLRRQAAIRTDSLDVQGLGSREDLLAEVSGPS PPLARAYSFWGQSSTQAQQHSRSHSKISKHMTPPAPCPGPEPNWGKGPPETRSSLELDTE LSWISGDLLPPGGQEEPPSPRDLKKCYSVEAQSCQRRPTSWLDEQRRHSIAVSCLDSGSQ PHLGTDPSNLGGQPLGGPGSRPKKKLSPPSITIDPPESQGPRTPPSPGICLRRRAPSSDS KDPLASGPPDSMAASPSPKKDVLSLSGLSSDPADLDP
Function	This transporter is voltage-sensitive calcium channels (VSCC), and it 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.
TCDB ID	8.B.5.1.1
Gene ID	8913
KEGG Pathway	MAPK signaling pathway (hsa04010 ) Calcium signaling pathway (hsa04020 ) Circadian entrainment (hsa04713 ) Aldosterone synthesis and secretion (hsa04925 ) Cortisol synthesis and secretion (hsa04927 ) GnRH secretion (hsa04929 ) Type II diabetes mellitus (hsa04930 ) Cushing syndrome (hsa04934 )
Reactome Pathway	NCAM1 interactions (R-HSA-419037 )

The Drug Therapeutic Target (DTT) Role of This DTP

DTP DTT Name

Voltage-gated calcium channel alpha Cav3.1 (CACNA1G) DTT Info

DTP DTT Type

Successful

6 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethosuximide	DMDZ9LT	Epilepsy	8A60-8A68	Approved	[1]
Methsuximide	DM6L5VO	Absence epilepsy		Approved	[2]
Paramethadione	DMR5ZUP	Absence epilepsy		Approved	[3]
Penfluridol	DMG1DTE	Schizophrenia	6A20	Approved	[4]
Trimethadione	DM0Q8MZ	Absence epilepsy		Approved	[3]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[5]
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⏷ Show the Full List of 6 Approved Drug(s)

2 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-200390	DMPW28M	Insomnia	7A00-7A0Z	Phase 2	[6]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[4]
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30 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-(R)-efonidipine	DMV6EMN	Discovery agent	N.A.	Investigative	[7]
Alpha-methyl-alpha-phenylsuccinimide (MPS)	DM892JF	Discovery agent	N.A.	Investigative	[2]
Cis-N,5-dibenzyl-6-oxomorpholine-3-carboxamide	DM75SO4	Discovery agent	N.A.	Investigative	[8]
KKHT-10318	DMAU1SZ	Discovery agent	N.A.	Investigative	[9]
KKHT-10608	DMYT381	Discovery agent	N.A.	Investigative	[9]
KKHT-10609	DMMI1H0	Discovery agent	N.A.	Investigative	[9]
KKHT-10613	DM1H5TO	Discovery agent	N.A.	Investigative	[9]
KKHT-10618	DMW704S	Discovery agent	N.A.	Investigative	[9]
KKHT-11018	DM4F96I	Discovery agent	N.A.	Investigative	[9]
KKHT-20718	DMLB4TU	Discovery agent	N.A.	Investigative	[9]
KKHT-20818	DMP1A3C	Discovery agent	N.A.	Investigative	[9]
KKHT-20918	DMTW4Q1	Discovery agent	N.A.	Investigative	[9]
KYS-05001	DM3MID9	Discovery agent	N.A.	Investigative	[10]
KYS-05040	DM1JU8F	Discovery agent	N.A.	Investigative	[11]
KYS-05041	DMVA6LH	Discovery agent	N.A.	Investigative	[12]
KYS-05042	DMM6G4H	Discovery agent	N.A.	Investigative	[13]
KYS-05050	DMXR3V4	Solid tumour/cancer	2A00-2F9Z	Investigative	[14]
KYS-05055	DMRVOT7	Discovery agent	N.A.	Investigative	[13]
KYS-05056	DMP6S0L	Discovery agent	N.A.	Investigative	[13]
KYS-05057	DM7BYG8	Discovery agent	N.A.	Investigative	[13]
KYS-05064	DM61GPQ	Discovery agent	N.A.	Investigative	[12]
KYS-05065	DMA8LFD	Discovery agent	N.A.	Investigative	[13]
KYS-05070	DMRJQY3	Discovery agent	N.A.	Investigative	[15]
KYS-05071	DM7K5Z3	Discovery agent	N.A.	Investigative	[15]
KYS-05074	DMYRWQ3	Discovery agent	N.A.	Investigative	[15]
KYS-05077	DMHW40F	Discovery agent	N.A.	Investigative	[14]
KYS-05080	DM57BXZ	Discovery agent	N.A.	Investigative	[13]
KYS-05090	DM92RHP	Discovery agent	N.A.	Investigative	[13]
ML218	DM3D21X	Discovery agent	N.A.	Investigative	[16]
Nickel chloride	DMI12Y8	Discovery agent	N.A.	Investigative	[17]
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⏷ Show the Full List of 30 Investigative Drug(s)

References

1	Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci. 2008 Nov 12;28(46):11959-69.
2	Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol. 2001 Nov;60(5):1121-32.
3	Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 2007 Apr;226(1-2):52-60.
4	Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci. 2002 Jan 15;22(2):396-403.
5	Mechanism of tissue-selective drug action in the cardiovascular system. Mol Interv. 2005 Apr;5(2):84-93.
6	Pfizer. Product Development Pipeline. March 31 2009.
7	Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels. Br J Pharmacol. 2004 Dec;143(8):1050-7.
8	Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8.
9	Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives. Bioorg Med Chem. 2007 Jan 1;15(1):365-73.
10	Discovery of potent T-type calcium channel blocker. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5740-3.
11	3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
12	3D pharmacophore based virtual screening of T-type calcium channel blockers. Bioorg Med Chem. 2007 Jan 15;15(2):1091-105.
13	T-type Ca2+ channel blockers suppress the growth of human cancer cells. Bioorg Med Chem Lett. 2008 Jul 15;18(14):3899-901.
14	Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
15	Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5014-7.
16	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.
17	T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting beta-cell line, INS-1. Endocrinology. 1997 Sep;138(9):3735-40.