Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAXZ0K)

• DTT Name: Voltage-gated sodium channel alpha Nav1.3 (SCN3A)
• Synonyms: Voltage-gated sodium channel subunit alpha Nav1.3; Voltage-gated sodium channel subtype III; Sodium channel protein, brain III subunit alpha; Sodium channel protein type III subunit alpha; Sodium channel protein type 3 subunit alpha; Sodium channel protein brain III subunit alpha; NAC3; KIAA1356
• Gene Name: SCN3A
• DTT Type: Successful target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: SCN3A_HUMAN
• TTD ID: T76937
• Sequence:
  MAQALLVPPGPESFRLFTRESLAAIEKRAAEEKAKKPKKEQDNDDENKPKPNSDLEAGKN
  LPFIYGDIPPEMVSEPLEDLDPYYINKKTFIVMNKGKAIFRFSATSALYILTPLNPVRKI
  AIKILVHSLFSMLIMCTILTNCVFMTLSNPPDWTKNVEYTFTGIYTFESLIKILARGFCL
  EDFTFLRDPWNWLDFSVIVMAYVTEFVSLGNVSALRTFRVLRALKTISVIPGLKTIVGAL
  IQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPPSDSAFETNTTSYFNGTMD
  SNGTFVNVTMSTFNWKDYIGDDSHFYVLDGQKDPLLCGNGSDAGQCPEGYICVKAGRNPN
  YGYTSFDTFSWAFLSLFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLVNLIL
  AVVAMAYEEQNQATLEEAEQKEAEFQQMLEQLKKQQEEAQAVAAASAASRDFSGIGGLGE
  LLESSSEASKLSSKSAKEWRNRRKKRRQREHLEGNNKGERDSFPKSESEDSVKRSSFLFS
  MDGNRLTSDKKFCSPHQSLLSIRGSLFSPRRNSKTSIFSFRGRAKDVGSENDFADDEHST
  FEDSESRRDSLFVPHRHGERRNSNVSQASMSSRMVPGLPANGKMHSTVDCNGVVSLVGGP
  SALTSPTGQLPPEGTTTETEVRKRRLSSYQISMEMLEDSSGRQRAVSIASILTNTMEELE
  ESRQKCPPCWYRFANVFLIWDCCDAWLKVKHLVNLIVMDPFVDLAITICIVLNTLFMAME
  HYPMTEQFSSVLTVGNLVFTGIFTAEMVLKIIAMDPYYYFQEGWNIFDGIIVSLSLMELG
  LSNVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVG
  MQLFGKSYKECVCKINDDCTLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQTMC
  LIVFMLVMVIGNLVVLNLFLALLLSSFSSDNLAATDDDNEMNNLQIAVGRMQKGIDYVKN
  KMRECFQKAFFRKPKVIEIHEGNKIDSCMSNNTGIEISKELNYLRDGNGTTSGVGTGSSV
  EKYVIDENDYMSFINNPSLTVTVPIAVGESDFENLNTEEFSSESELEESKEKLNATSSSE
  GSTVDVVLPREGEQAETEPEEDLKPEACFTEGCIKKFPFCQVSTEEGKGKIWWNLRKTCY
  SIVEHNWFETFIVFMILLSSGALAFEDIYIEQRKTIKTMLEYADKVFTYIFILEMLLKWV
  AYGFQTYFTNAWCWLDFLIVDVSLVSLVANALGYSELGAIKSLRTLRALRPLRALSRFEG
  MRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCVNMTTGNMFDISDVNN
  LSDCQALGKQARWKNVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRDVKLQPVYEE
  NLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLG
  SKKPQKPIPRPANKFQGMVFDFVTRQVFDISIMILICLNMVTMMVETDDQGKYMTLVLSR
  INLVFIVLFTGEFVLKLVSLRHYYFTIGWNIFDFVVVILSIVGMFLAEMIEKYFVSPTLF
  RVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYV
  KKEAGIDDMFNFETFGNSMICLFQITTSAGWDGLLAPILNSAPPDCDPDTIHPGSSVKGD
  CGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFEMFYEVWEKF
  DPDATQFIEFSKLSDFAAALDPPLLIAKPNKVQLIAMDLPMVSGDRIHCLDILFAFTKRV
  LGESGEMDALRIQMEDRFMASNPSKVSYEPITTTLKRKQEEVSAAIIQRNFRCYLLKQRL
  KNISSNYNKEAIKGRIDLPIKQDMIIDKLNGNSTPEKTDGSSSTTSPPSYDSVTKPDKEK
  FEKDKPEKESKGKEVRENQK
• Function: Assuming opened or closed conformations in response to the voltage difference across the membrane, forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. May contribute to the regulation of serotonin/5-hydroxytryptamine release by enterochromaffin cells. In pancreatic endocrine cells, required for both glucagon and glucose-induced insulin secretion. Mediates the voltage-dependent sodium ion permeability of excitable membranes.
• KEGG Pathway: Taste transduction (hsa04742)
• Reactome Pathway: Interaction between L1 and Ankyrins (R-HSA-445095)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIDOFLAZINE	DMV23GL	Angina pectoris	BA40	Approved	[1]

5 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aryl carboxamide derivative 1	DMTZRCW	N. A.	N. A.	Patented	[2]
Aryl carboxamide derivative 2	DM146TA	N. A.	N. A.	Patented	[2]
Pyrimidine derivative 1	DMN9VQM	N. A.	N. A.	Patented	[2]
Pyrrolo-pyridinone derivative 5	DMK2FSY	N. A.	N. A.	Patented	[2]
Pyrrolo-pyridinone derivative 6	DMXGNP8	N. A.	N. A.	Patented	[2]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SIPATRIGINE	DMMQ4GC	Neurological disorder	6B60	Discontinued in Phase 2	[3]
PD-85639	DMNUKB4	N. A.	N. A.	Terminated	[1]
U-92032	DMTYO3P	N. A.	N. A.	Terminated	[4]

18 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(1-Pentyl-hexyl)-4-phenyl-1H-imidazole	DMR0HDF	Discovery agent	N.A.	Investigative	[5]
2-Hexyl-4-(4-isobutyl-phenyl)-1H-imidazole	DM94PBL	Discovery agent	N.A.	Investigative	[5]
2-Hydroxy-2-phenyl-nonanoic acid amide	DM2GPF6	Discovery agent	N.A.	Investigative	[6]
4-Biphenyl-4-yl-2-(1-pentyl-hexyl)-1H-imidazole	DML6PTX	Discovery agent	N.A.	Investigative	[5]
4-Biphenyl-4-yl-2-(1-propyl-butyl)-1H-imidazole	DM2I13S	Discovery agent	N.A.	Investigative	[5]
4-Biphenyl-4-yl-2-cyclohexylmethyl-1H-imidazole	DMLSUXD	Discovery agent	N.A.	Investigative	[5]
4-Biphenyl-4-yl-2-hexyl-1H-imidazole	DMPIH4L	Discovery agent	N.A.	Investigative	[5]
4-Biphenyl-4-yl-2-methyl-1H-imidazole	DMNLC2Y	Discovery agent	N.A.	Investigative	[5]
5-Ethyl-3-methyl-5-phenyl-oxazolidine-2,4-dione	DMYD8GP	Discovery agent	N.A.	Investigative	[7]
5-Heptyl-5-phenyl-imidazolidine-2,4-dione	DMICKOU	Discovery agent	N.A.	Investigative	[6]
5-Hexyl-5-phenyl-imidazolidine-2,4-dione	DMCDUO1	Discovery agent	N.A.	Investigative	[6]
5-Nonyl-5-phenyl-imidazolidine-2,4-dione	DM2DWUQ	Discovery agent	N.A.	Investigative	[6]
batrachotoxin	DMYH9SU	Discovery agent	N.A.	Investigative	[8]
BW-202W92	DMFKXMT	Discovery agent	N.A.	Investigative	[9]
CCNCSSKWCRDHSRCC	DMBGHTW	Discovery agent	N.A.	Investigative	[10]
L-741742	DMP75YK	Discovery agent	N.A.	Investigative	[11]
RQ-00203066	DMAIOQB	Pain	MG30-MG3Z	Investigative	[8]
veratridine	DMUF8JZ	Discovery agent	N.A.	Investigative	[8]

References

• [1] Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
• [2] Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90.
• [3] Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke. J Med Chem. 2002 Aug 15;45(17):3755-64.
• [4] 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.
• [5] 2-Alkyl-4-arylimidazoles: structurally novel sodium channel modulators. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3521-3.
• [6] Comparative molecular field analysis of hydantoin binding to the neuronal voltage-dependent sodium channel. J Med Chem. 1999 May 6;42(9):1537-45.
• [7] Sodium channel binding and anticonvulsant activities for the enantiomers of a bicyclic 2,4-oxazolidinedione and monocyclic models. J Med Chem. 1989 Jul;32(7):1577-80.
• [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: 580).
• [9] Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
• [10] Structure/function characterization of micro-conotoxin KIIIA, an analgesic, nearly irreversible blocker of mammalian neuronal sodium channels. J Biol Chem. 2007 Oct 19;282(42):30699-706.
• [11] 1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) rece... J Med Chem. 1999 Jul 15;42(14):2706-15.