Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT84DRB)

• DTT Name: Voltage-gated sodium channel alpha Nav1.4 (SCN4A)
• Synonyms: Voltage-gated sodium channel subunit alpha Nav1.4; Sodium channel protein type IV subunit alpha; Sodium channel protein skeletal muscle subunit alpha; SkM1; SCN4A
• Gene Name: SCN4A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: SCN4A_HUMAN
• TTD ID: T02546
• Sequence:
  MARPSLCTLVPLGPECLRPFTRESLAAIEQRAVEEEARLQRNKQMEIEEPERKPRSDLEA
  GKNLPMIYGDPPPEVIGIPLEDLDPYYSNKKTFIVLNKGKAIFRFSATPALYLLSPFSVV
  RRGAIKVLIHALFSMFIMITILTNCVFMTMSDPPPWSKNVEYTFTGIYTFESLIKILARG
  FCVDDFTFLRDPWNWLDFSVIMMAYLTEFVDLGNISALRTFRVLRALKTITVIPGLKTIV
  GALIQSVKKLSDVMILTVFCLSVFALVGLQLFMGNLRQKCVRWPPPFNDTNTTWYSNDTW
  YGNDTWYGNEMWYGNDSWYANDTWNSHASWATNDTFDWDAYISDEGNFYFLEGSNDALLC
  GNSSDAGHCPEGYECIKTGRNPNYGYTSYDTFSWAFLALFRLMTQDYWENLFQLTLRAAG
  KTYMIFFVVIIFLGSFYLINLILAVVAMAYAEQNEATLAEDKEKEEEFQQMLEKFKKHQE
  ELEKAKAAQALEGGEADGDPAHGKDCNGSLDTSQGEKGAPRQSSSGDSGISDAMEELEEA
  HQKCPPWWYKCAHKVLIWNCCAPWLKFKNIIHLIVMDPFVDLGITICIVLNTLFMAMEHY
  PMTEHFDNVLTVGNLVFTGIFTAEMVLKLIAMDPYEYFQQGWNIFDSIIVTLSLVELGLA
  NVQGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQ
  LFGKSYKECVCKIALDCNLPRWHMHDFFHSFLIVFRILCGEWIETMWDCMEVAGQAMCLT
  VFLMVMVIGNLVVLNLFLALLLSSFSADSLAASDEDGEMNNLQIAIGRIKLGIGFAKAFL
  LGLLHGKILSPKDIMLSLGEADGAGEAGEAGETAPEDEKKEPPEEDLKKDNHILNHMGLA
  DGPPSSLELDHLNFINNPYLTIQVPIASEESDLEMPTEEETDTFSEPEDSKKPPQPLYDG
  NSSVCSTADYKPPEEDPEEQAEENPEGEQPEECFTEACVQRWPCLYVDISQGRGKKWWTL
  RRACFKIVEHNWFETFIVFMILLSSGALAFEDIYIEQRRVIRTILEYADKVFTYIFIMEM
  LLKWVAYGFKVYFTNAWCWLDFLIVDVSIISLVANWLGYSELGPIKSLRTLRALRPLRAL
  SRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYYCINTTTSERFDI
  SEVNNKSECESLMHTGQVRWLNVKVNYDNVGLGYLSLLQVATFKGWMDIMYAAVDSREKE
  EQPQYEVNLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGKDIFMTEEQKKYY
  NAMKKLGSKKPQKPIPRPQNKIQGMVYDLVTKQAFDITIMILICLNMVTMMVETDNQSQL
  KVDILYNINMIFIIIFTGECVLKMLALRQYYFTVGWNIFDFVVVILSIVGLALSDLIQKY
  FVSPTLFRVIRLARIGRVLRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFG
  MSNFAYVKKESGIDDMFNFETFGNSIICLFEITTSAGWDGLLNPILNSGPPDCDPNLENP
  GTSVKGDCGNPSIGICFFCSYIIISFLIVVNMYIAIILENFNVATEESSEPLGEDDFEMF
  YETWEKFDPDATQFIAYSRLSDFVDTLQEPLRIAKPNKIKLITLDLPMVPGDKIHCLDIL
  FALTKEVLGDSGEMDALKQTMEEKFMAANPSKVSYEPITTTLKRKHEEVCAIKIQRAYRR
  HLLQRSMKQASYMYRHSHDGSGDDAPEKEGLLANTMSKMYGHENGNSSSPSPEEKGEAGD
  AGPTMGLMPISPSDTAWPPAPPPGQTVRPGVKESLV
• Function: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
• Reactome Pathway: Interaction between L1 and Ankyrins (R-HSA-445095)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lanperisone	DM4EGPN	Musculoskeletal disorder	FA00-FC0Z	Phase 3	[1]

2 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	[2]
V-102862	DMR2EUV	N. A.	N. A.	Discontinued in Phase 1	[3]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(4-Phenoxy-phenyl)-1H-pyrazole	DMO6LID	Discovery agent	N.A.	Investigative	[3]
3-[4-(4-Fluoro-phenoxy)-phenyl]-1H-pyrazole	DME86OK	Discovery agent	N.A.	Investigative	[3]
batrachotoxin	DMYH9SU	Discovery agent	N.A.	Investigative	[4]
BW-202W92	DMFKXMT	Discovery agent	N.A.	Investigative	[2]
CCACSSKWCRDHSRCC	DMSE20Y	Discovery agent	N.A.	Investigative	[5]
CCNCASKWCRDHSRCC	DMRFA5O	Discovery agent	N.A.	Investigative	[5]
CCNCSAKWCRDHSRCC	DMZKJ37	Discovery agent	N.A.	Investigative	[5]
CCNCSSKWCRAHSRCC	DM96YR2	Discovery agent	N.A.	Investigative	[5]
CCNCSSKWCRDHARCC	DMP0C7B	Discovery agent	N.A.	Investigative	[5]
CCNCSSKWCRDHSRCC	DMBGHTW	Discovery agent	N.A.	Investigative	[5]
grayanotoxin III	DMXSWF6	Discovery agent	N.A.	Investigative	[6]
veratridine	DMUF8JZ	Discovery agent	N.A.	Investigative	[4]
XEP-018	DMVTCZ1	Pain	MG30-MG3Z	Investigative	[7]
ZNCCNCSSKWCRDHSRCC	DMY2V37	Discovery agent	N.A.	Investigative	[5]
ZRCCNCSSKWCRDHSRCC	DM1YZJ3	Discovery agent	N.A.	Investigative	[5]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Voltage-gated sodium channel alpha Nav1.4 (SCN4A) DTP Info
• Gene Name: SCN4A

References

• [1] Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels. J Pharmacol Exp Ther. 2005 Dec;315(3):1237-46.
• [2] Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
• [3] 3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers. J Med Chem. 2004 Mar 11;47(6):1547-52.
• [4] Point mutations in segment I-S6 render voltage-gated Na+ channels resistant to batrachotoxin. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2653-8.
• [5] 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.
• [6] Novel site on sodium channel alpha-subunit responsible for the differential sensitivity of grayanotoxin in skeletal and cardiac muscle. Mol Pharmacol. 2001 Oct;60(4):865-72.
• [7] 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: 581).