Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT7SZIQ)

• DTP Name: Voltage-gated sodium channel alpha Nav1.4 (SCN4A)
• Gene Name: SCN4A
• UniProt ID: P35499 (SCN4A_HUMAN)
• VARIDT ID: DTD0527
• Synonyms: CMS16; HOKPP2; HYKPP; HYPP; NAC1A; Na(V)1.4; Nav1.4; SCN4A; SkM1; Sodium channel protein skeletal muscle subunit alpha; Sodium channel protein type IV subunit alpha; Sodium channel protein type 4 subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.4
• DTP Family: Voltage-Gated Ion Channel (VIC) Superfamily
• 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 pore-forming subunit of a voltage-gated transporter complex mediates the transport of Na(+) ions pass in accordance with their electrochemical gradient. Alternates between resting, activated and inactivated states. Required for normal muscle fiber excitability, normal muscle contraction and relaxation cycles, and constant muscle strength in the presence of fluctuating K(+) levels.
• Endogenous Substrate(s): Na+
• TCDB ID: 1.A.1.10.4
• Gene ID: 6329
• Reactome Pathway:
  Phase 0 - rapid depolarisation (R-HSA-5576892)
  Interaction between L1 and Ankyrins (R-HSA-445095)

The Drug Therapeutic Target (DTT) Role of This DTP

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

1 Clinical Trial Drug(s) Targeting This DTP

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 DTP

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 DTP

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]

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).