Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTQC85B)

• DTP Name: Voltage-gated sodium channel alpha Nav1.7 (SCN9A)
• Gene Name: SCN9A
• UniProt ID: Q15858 (SCN9A_HUMAN)
• VARIDT ID: DTD0529
• Synonyms: ETHA; FEB3B; GEFSP7; HSAN2D; NE-NA; NENA; Nav1.7; Neuroendocrine sodium channel; PN1; Peripheral sodium channel 1; SCN9A; SFNP; Sodium channel protein type IX subunit alpha; Sodium channel protein type 9 subunit alpha; hNE-Na; Voltage-gated sodium channel subunit alpha Nav1.7
• DTP Family: Voltage-Gated Ion Channel (VIC) Superfamily
• Tissue Specificity: Expressed strongly in dorsal root ganglion,with only minor levels elsewhere in the body, smooth muscle cells,MTC cell line and C-cell carcinoma. Isoform 1 is expressedpreferentially in the central and peripheral nervous system.Isoform 2 is expressed preferentially in the dorsal root ganglion.
• Sequence:
  MAMLPPPGPQSFVHFTKQSLALIEQRIAERKSKEPKEEKKDDDEEAPKPSSDLEAGKQLP
  FIYGDIPPGMVSEPLEDLDPYYADKKTFIVLNKGKTIFRFNATPALYMLSPFSPLRRISI
  KILVHSLFSMLIMCTILTNCIFMTMNNPPDWTKNVEYTFTGIYTFESLVKILARGFCVGE
  FTFLRDPWNWLDFVVIVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQ
  SVKKLSDVMILTVFCLSVFALIGLQLFMGNLKHKCFRNSLENNETLESIMNTLESEEDFR
  KYFYYLEGSKDALLCGFSTDSGQCPEGYTCVKIGRNPDYGYTSFDTFSWAFLALFRLMTQ
  DYWENLYQQTLRAAGKTYMIFFVVVIFLGSFYLINLILAVVAMAYEEQNQANIEEAKQKE
  LEFQQMLDRLKKEQEEAEAIAAAAAEYTSIRRSRIMGLSESSSETSKLSSKSAKERRNRR
  KKKNQKKLSSGEEKGDAEKLSKSESEDSIRRKSFHLGVEGHRRAHEKRLSTPNQSPLSIR
  GSLFSARRSSRTSLFSFKGRGRDIGSETEFADDEHSIFGDNESRRGSLFVPHRPQERRSS
  NISQASRSPPMLPVNGKMHSAVDCNGVVSLVDGRSALMLPNGQLLPEVIIDKATSDDSGT
  TNQIHKKRRCSSYLLSEDMLNDPNLRQRAMSRASILTNTVEELEESRQKCPPWWYRFAHK
  FLIWNCSPYWIKFKKCIYFIVMDPFVDLAITICIVLNTLFMAMEHHPMTEEFKNVLAIGN
  LVFTGIFAAEMVLKLIAMDPYEYFQVGWNIFDSLIVTLSLVELFLADVEGLSVLRSFRLL
  RVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKIN
  DDCTLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVYMMVMVIGNLVVL
  NLFLALLLSSFSSDNLTAIEEDPDANNLQIAVTRIKKGINYVKQTLREFILKAFSKKPKI
  SREIRQAEDLNTKKENYISNHTLAEMSKGHNFLKEKDKISGFGSSVDKHLMEDSDGQSFI
  HNPSLTVTVPIAPGESDLENMNAEELSSDSDSEYSKVRLNRSSSSECSTVDNPLPGEGEE
  AEAEPMNSDEPEACFTDGCVWRFSCCQVNIESGKGKIWWNIRKTCYKIVEHSWFESFIVL
  MILLSSGALAFEDIYIERKKTIKIILEYADKIFTYIFILEMLLKWIAYGYKTYFTNAWCW
  LDFLIVDVSLVTLVANTLGYSDLGPIKSLRTLRALRPLRALSRFEGMRVVVNALIGAIPS
  IMNVLLVCLIFWLIFSIMGVNLFAGKFYECINTTDGSRFPASQVPNRSECFALMNVSQNV
  RWKNLKVNFDNVGLGYLSLLQVATFKGWTIIMYAAVDSVNVDKQPKYEYSLYMYIYFVVF
  IIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRP
  GNKIQGCIFDLVTNQAFDISIMVLICLNMVTMMVEKEGQSQHMTEVLYWINVVFIILFTG
  ECVLKLISLRHYYFTVGWNIFDFVVVIISIVGMFLADLIETYFVSPTLFRVIRLARIGRI
  LRLVKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMSNFAYVKKEDGINDMFN
  FETFGNSMICLFQITTSAGWDGLLAPILNSKPPDCDPKKVHPGSSVEGDCGNPSVGIFYF
  VSYIIISFLVVVNMYIAVILENFSVATEESTEPLSEDDFEMFYEVWEKFDPDATQFIEFS
  KLSDFAAALDPPLLIAKPNKVQLIAMDLPMVSGDRIHCLDILFAFTKRVLGESGEMDSLR
  SQMEERFMSANPSKVSYEPITTTLKRKQEDVSATVIQRAYRRYRLRQNVKNISSIYIKDG
  DRDDDLLNKKDMAFDNVNENSSPEKTDATSSTTSPPSYDSVTKPDKEKYEQDRTEKEDKG
  KDSKESKK
• Function: This transporter plays a role in inflammatory pain mechanisms and 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. It is a tetrodotoxin-sensitive Na(+) channel isoform).
• Endogenous Substrate(s): Na+
• TCDB ID: 1.A.1.10.5
• Gene ID: 6335
• Reactome Pathway:
  Phase 0 - rapid depolarisation (R-HSA-5576892)
  Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207)
  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 Nav1.7 (SCN9A) DTT Info
• DTP DTT Type: Clinical trial
• Related Disease:
  Bipolar disorder [ICD-11: 6A60]
  Extremities vasodilatation [ICD-11: EG00]
  Osteoarthritis [ICD-11: FA00-FA05]
  Radiculopathy [ICD-11: 8B93]
  Trigeminal nerve disorder [ICD-11: 8B82]
  Chronic pain [ICD-11: MG30]
  General pain disorder [ICD-11: 8E43]
  Pain [ICD-11: MG30-MG3Z]

12 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BIIB074	DMLV1ET	Bipolar disorder	6A60	Phase 2	[1], [2]
PF-05089771	DMD74BJ	Chronic pain	MG30	Phase 2	[3]
XEN-402	DMR69CG	Osteoarthritis	FA00-FA05	Phase 2	[4]
BIIB095	DMUC6EP	Pain	MG30-MG3Z	Phase 1	[1]
CC8464	DMILHMC	Neuropathic pain	8E43.0	Phase 1	[1]
DSP-2230	DM0WTMD	Neuropathic pain	8E43.0	Phase 1	[1], [2]
DSP-3905	DMYHU24	Neuropathic pain	8E43.0	Phase 1	[1]
DWJ-208	DMQKDJZ	Cancer related pain	MG30	Phase 1	[1]
GDC0310	DMUNFEP	Chronic pain	MG30	Phase 1	[2]
PF-05186462	DMUF6W9	Pain	MG30-MG3Z	Phase 1	[5]
PF-05241328	DM2NTBL	Pain	MG30-MG3Z	Phase 1	[6]
RG7893	DM1R4MQ	Pain	MG30-MG3Z	Phase 1	[7], [8]

19 Patented Agent(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aryl carboxamide derivative 1	DMTZRCW	N. A.	N. A.	Patented	[9]
Aryl carboxamide derivative 2	DM146TA	N. A.	N. A.	Patented	[9]
Aryl carboxamide derivative 4	DMNBW8P	N. A.	N. A.	Patented	[9]
Benzene sulfonamide derivative 11	DML9TF7	N. A.	N. A.	Patented	[9]
Benzene sulfonamide derivative 12	DMESKY1	N. A.	N. A.	Patented	[9]
Benzene sulfonamide derivative 15	DMFJTE9	N. A.	N. A.	Patented	[9]
Benzene sulfonamide derivative 9	DMLET14	N. A.	N. A.	Patented	[9]
Cyclopropyl-spiro piperidine derivative 1	DM0YTGS	N. A.	N. A.	Patented	[9]
Cyclopropyl-spiro piperidine derivative 2	DMM0R65	N. A.	N. A.	Patented	[9]
Cyclopropyl-spiro piperidine derivative 3	DM0IZW8	N. A.	N. A.	Patented	[9]
Cyclopropyl-spiro piperidine derivative 4	DM2ZWSM	N. A.	N. A.	Patented	[9]
Dihydrobenzoxazine and tetrahydroquinoxaline sulfonamide derivative 1	DMUNFAT	N. A.	N. A.	Patented	[9]
Enzoxazolinone sulfonamide derivative 1	DMJSIN8	N. A.	N. A.	Patented	[9]
Methylsulfonylbenzamide derivative 2	DMHVZ4M	N. A.	N. A.	Patented	[9]
Pyrimidine derivative 1	DMN9VQM	N. A.	N. A.	Patented	[9]
Pyrrolo-benzo-diazine derivative 1	DMS4I6B	N. A.	N. A.	Patented	[9]
Pyrrolo-pyridinone derivative 5	DMK2FSY	N. A.	N. A.	Patented	[9]
Pyrrolo-pyridinone derivative 6	DMXGNP8	N. A.	N. A.	Patented	[9]
Tarizine derivative 1	DMK5HAC	N. A.	N. A.	Patented	[9]

3 Discontinued Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Corus 1030	DMRVJ1A	Asthma	CA23	Discontinued in Phase 2	[10], [11]
Sipatrigine	DMMQ4GC	Neurological disorder	6B60	Discontinued in Phase 2	[12]
V-102862	DMR2EUV	N. A.	N. A.	Discontinued in Phase 1	[13]

8 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(2'-(trifluoromethoxy)biphenyl-3-yl)oxazole	DMIL45X	Discovery agent	N.A.	Investigative	[13]
4-(2'-(trifluoromethoxy)biphenyl-3-yl)thiazole	DM3R2D1	Discovery agent	N.A.	Investigative	[13]
4-(2'-(trifluoromethyl)biphenyl-3-yl)oxazole	DMXC5S0	Discovery agent	N.A.	Investigative	[13]
Batrachotoxin	DMYH9SU	Discovery agent	N.A.	Investigative	[14]
N-Me-aminopyrimidinone 9	DMM731A	Discovery agent	N.A.	Investigative	[15]
pyrrolopyrimidine 48	DMUEKB3	Discovery agent	N.A.	Investigative	[16]
Veratridine	DMUF8JZ	Discovery agent	N.A.	Investigative	[14]
XEN-907	DMZ24P1	Pain	MG30-MG3Z	Investigative	[14]

References

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• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Primary erythromelalgia: a review. Orphanet J Rare Dis. 2015 Sep 30;10:127.
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• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026875)
• [6] Recent progress in sodium channel modulators for pain. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3690-9.
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800041740)
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90.
• [10] Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol. 2004 Jun;142(3):576-84.
• [11] Lidocaine reduces the transition to slow inactivation in Na(v)1.7 voltage-gated sodium channels.Br J Pharmacol.2011 Sep;164(2b):719-30.
• [12] Oxadiazolylindazole sodium channel modulators are neuroprotective toward hippocampal neurones. J Med Chem. 2009 May 14;52(9):2694-707.
• [13] Substituted biaryl oxazoles, imidazoles, and thiazoles as sodium channel blockers. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5536-40.
• [14] 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: 584).
• [15] Discovery and optimization of aminopyrimidinones as potent and state-dependent Nav1.7 antagonists. Bioorg Med Chem Lett. 2012 Jan 15;22(2):1055-60.
• [16] Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state-dependent Na(v)1.7 antagonists. Bioorg Med Chem Lett. 2012 Mar 1;22(5):2052-62.