| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:07:50 |
| Primary Accession Number |
DB00740 |
| Secondary Accession Number |
|
| Name |
Riluzole |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| Description |
A glutamate antagonist (receptors, glutamate) used as an anticonvulsant (anticonvulsants) and to prolong the survival of patients with amyotrophic lateral sclerosis. [PubChem] |
| Synonyms |
- riluzole
|
| Brand Names |
- Rilutek
- Riluzole HCl
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
6-(trifluoromethoxy)-1,3-benzothiazol-2-amine |
| Chemical Formula |
C8H5F3N2OS |
| Chemical Structure |
 |
| CAS Registry Number |
1744-22-5 |
| InChI Identifier |
InChI=1/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)/f/h12H2 |
| InChI Key |
FTALBRSUTCGOEG-GAJRPKRDCG |
| KEGG Drug |
D00775  |
| KEGG Compound |
C07937  |
| PubChem Compound |
5070  |
| PubChem Substance |
7847840  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA451251  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02242763  |
| RxList Link |
http://www.rxlist.com/cgi/generic3/riluzole.htm  |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Riluzole  |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
Not Available |
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
234.1980 |
| Monoisotopic Molecular Weight |
234.0075 |
| State |
Solid |
| Melting Point |
119 oC |
| Experimental Water Solubility |
Not Available
Source: PhysProp
|
| Predicted Water Solubility |
3.95e-02 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
2.3
Source: PhysProp
|
| Predicted LogP |
2.83
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-3.77
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
NC1=NC2=C(S1)C=C(OC(F)(F)F)C=C2 |
| Canonical SMILES |
NC1=NC2=C(S1)C=C(OC(F)(F)F)C=C2 |
| Drug Category |
- Anesthetics
- Anticonvulsants
- Excitatory Amino Acid Antagonists
- Neuroprotective Agents
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease) |
| Pharmacology |
Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective. |
| Mechanism of Action |
The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors. |
| Absorption |
Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%. |
| Toxicity |
Not Available |
| Protein Binding |
96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range. |
| Biotransformation |
Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans. |
| Half Life |
The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses. |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
Not Available
|
| Food Interactions |
- Take on an empty stomach 1 hour before or 2 hours after meals.
|
| Pathways |
Not Available
|
| General References |
- Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004 Jan;161(1):171-4. [PubMed
]
- van Kan HJ, Groeneveld GJ, Kalmijn S, Spieksma M, van den Berg LH, Guchelaar HJ: Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol. 2005 Mar;59(3):310-3. [PubMed
]
- Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH: Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. [PubMed
]
- Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T: Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther. 1997 Aug;282(2):707-14. [PubMed
]
- Drugs.com

- Wikipedia

- RxList

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 1A2 (CYP1A2)
|
| Targets |
- Sodium channel protein type 5 subunit alpha
- Glutamate [NMDA] receptor subunit 3A
|
|
Drug Target 1
[top]
|
| Target 1 ID |
220 |
| Target 1 Name |
Sodium channel protein type 5 subunit alpha |
| Target 1 Synonyms |
- HH1
- Sodium channel protein type V subunit alpha
- Sodium channel protein, cardiac muscle alpha-subunit
- Voltage-gated sodium channel subunit alpha Nav1.5
|
| Target 1 Gene Name |
SCN5A |
| Target 1 Protein Sequence |
>Sodium channel protein type 5 subunit alpha
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQA
SKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPV
RRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARA
FCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV
GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLV
WESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAW
AFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQN
QATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK
RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSE
ADFADDENSTARESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGV
VSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQ
RALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD
LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQG
WNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALG
NLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWI
ETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ
LALARIQRGLRFVKRTTWDFCCGLLRHRPQKPAALAAQGQLPSCIATPYSPPPPETEKVP
PTRKETQFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQ
PVSGWPRGPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGS
TADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH
IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVA
YGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGM
RVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNN
KSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW
EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKK
LGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINIL
AKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPT
LFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA
YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRG
DCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEK
FDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKR
VLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS
LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSV
TRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV
|
| Target 1 Number of Residues |
2049 |
| Target 1 Molecular Weight |
227165 |
| Target 1 Theoretical pI |
5.23 |
| Target 1 GO Classification |
|
Function
|
voltage-gated ion channel activity
voltage-gated sodium channel activity
transporter activity
ion transporter activity
ion channel activity |
|
Process
|
cation transport
monovalent inorganic cation transport
sodium ion transport
physiological process
cellular physiological process
transport
ion transport |
|
Component
|
protein complex
voltage-gated sodium channel complex
cell
membrane |
|
| Target 1 General Function |
Involved in ion channel activity |
| Target 1 Specific 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. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 127-150
- 159-178
- 192-210
- 217-236
- 253-276
- 390-415
- 712-736
- 748-771
- 780-799
- 806-825
- 842-862
- 914-939
- 1201-1224
- 1238-1263
- 1270-1291
- 1296-1317
- 1337-1359
- 1444-1470
- 1524-1547
- 1559-1582
- 1589-1612
- 1623-1644
- 1660-1682
- 1748-1772
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
184039  |
| Target 1 UniProtKB/Swiss-Prot ID |
Q14524  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
SCN5A_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>6051 bp
ATGGCAAACTTCCTATTACCTCGGGGCACCAGCAGCTTCCGCAGGTTCACACGGGAGTCC
CTGGCAGCCATCGAGAAGCGCATGGCGGAGAAGCAAGCCCGCGGCTCAACCACCTTGCAG
GAGAGCCGAGAGGGGCTGCCCGAGGAGGAGGCTCCCCGGCCCCAGCTGGACCTGCAGGCC
TCCAAAAAGCTGCCAGATCTCTATGGCAATCCACCCCAAGAGCTCATCGGAGAGCCCCTG
GAGGACCTGGACCCCTTCTATAGCACCCAAAAGACTTTCATCGTACTGAATAAAGGCAAG
ACCATCTTCCGGTTCAGTGCCACCAACGCCTTGTATGTCCTCAGTCCCTTCCACCCAGTT
CGGAGAGCGGCTGTGAAGATTCTGGTTCACTCGCTCTTCAACATGCTCATCATGTGCACC
ATCCTCACCAACTGCGTGTTCATGGCCCAGCACGACCCTCCACCCTGGACCAAGTATGTC
GAGTACACCTTCACCGCCATTTACACCTTTGAGTCTCTGGTCAAGATTCTGGCTCGAGCT
TTCTGCCTGCACGCGTTCACTTTCCTTCGGGACCCATGGAACTGGCTGGACTTTAGTGTG
ATTATCATGGCATACACAACTGAATTTGTGGACCTGGGCAATGTCTCAGCCTTACGCACC
TTCCGAGTCCTCCGGGCCCTGAAAACTATATCAGTCATTTCAGGGCTGAAGACCATCGTG
GGGGCCCTGATCCAGTCTGTGAAGAAGCTGGCTGATGTGATGGTCCTCACAGTCTTCTGC
CTCAGCGTCTTTGCCCTCATCGGCCTGCAGCTCTTCATGGGCAACCTAAGGCACAAGTGT
GTGCGCAACTTCACAGCGCTCAACGGCACCAACGGCTCCGTGGAGGCCGACGGCTTGGTC
TGGGAATCCCTGGACCTTTACCTCAGTGATCCAGAAAATTACCTGCTCAAGAACGGCACC
TCTGATGTGTTACTGTGTGGGAACAGCTCTGACGCTGGGACATGTCCGGAGGGCTACCGG
TGCCTAAAGGCAGGCGAGAACCCCGACCACGGCTACACCAGCTTCGATTCCTTTGCCTGG
GCCTTTCTTGCACTCTTCCGCCTGATGACGCAGGACTGCTGGGAGCGCCTCTATCAGCAG
ACCCTCAGGTCCGCAGGGAAGATCTACATGATCTTCTTCATGCTTGTCATCTTCCTGGGG
TCCTTCTACCTGGTGAACCTGATCCTGGCCGTGGTCGCAATGGCCTATGAGGAGCAAAAC
CAAGCCACCATCGCTGAGACCGAGGAGAAGGAAAAGCGCTTCCAGGAGGCCATGGAAATG
CTCAAGAAAGAACACGAGGCCCTCACCATCAGGGGTGTGGATACCGTGTCCCGTAGCTCC
TTGGAGATGTCCCCTTTGGCCCCAGTAAACAGCCATGAGAGAAGAAGCAAGAGGAGAAAA
CGGATGTCTTCAGGAACTGAGGAGTGTGGGGAGGACAGGCTCCCCAAGTCTGACTCAGAA
GATGGTCCCAGAGCAATGAATCATCTCAGCCTCACCCGTGGCCTCAGCAGGACTTCTATG
AAGCCACGTTCCAGCCGCGGGAGCATTTTCACCTTTCGCAGGCGAGACCTGGGTTCTGAA
GCAGATTTTGCAGATGATGAAAACAGCACAGCGCGGGAGAGCGAGAGCCACCACACATCA
CTGCTGGTGCCCTGGCCCCTGCGCCGGACCAGTGCCCAGGGACAGCCCAGTCCCGGAACC
TCGGCTCCTGGCCACGCCCTCCATGGCAAAAAGAACAGCACTGTGGACTGCAATGGGGTG
GTCTCATTACTGGGGGCAGGCGACCCAGAGGCCACATCCCCAGGAAGCCACCTCCTCCGC
CCTGTGATGCTAGAGCACCCGCCAGACACGACCACGCCATCGGAGGAGCCAGGCGGCCCC
CAGATGCTGACCTCCCAGGCTCCGTGTGTAGATGGCTTCGAGGAGCCAGGAGCACGGCAG
CGGGCCCTCAGCGCAGTCAGCGTCCTCACAAGCGCACTGGAAGAGTTAGAGGAGTCTCGC
CACAAGTGTCCACCATGCTGGAACCGTCTCGCCCAGCGCTACCTGATCTGGGAGTGCTGC
CCGCTGTGGATGTCCATCAAGCAGGGAGTGAAGTTGGTGGTCATGGACCCGTTTACTGAC
CTCACCATCACTATGTGCATCGTACTCAACACACTCTTCATGGCGCTGGAGCACTACAAC
ATGACAAGTGAATTCGAGGAGATGCTGCAGGTCGGAAACCTGGTCTTCACAGGGATTTTC
ACAGCAGAGATGACCTTCAAGATCATTGCCCTCGACCCCTACTACTACTTCCAACAGGGC
TGGAACATCTTCGACAGCATCATCGTCATCCTTAGCCTCATGGAGCTGGGCCTGTCCCGC
ATGAGCAACTTGTCGGTGCTGCGCTCCTTCCGCCTGCTGCGGGTCTTCAAGCTGGCCAAA
TCATGGCCCACCCTGAACACACTCATCAAGATCATCGGGAACTCAGTGGGGGCACTGGGG
AACCTGACACTGGTGCTAGCCATCATCGTGTTCATCTTTGCTGTGGTGGGCATGCAGCTC
TTTGGCAAGAACTACTCGGAGCTGAGGGACAGCGACTCAGGCCTGCTGCCTCGCTGGCAC
ATGATGGACTTCTTTCATGCCTTCCTAATCATCTTCCGCATCCTCTGTGGAGAGTGGATC
GAGACCATGTGGGACTGCATGGAGGTGTCGGGGCAGTCATTATGCCTGCTGGTCTTCTTG
CTTGTTATGGTCATTGGCAACCTTGTGGTCCTGAATCTCTTCCTGGCCTTGCTGCTCAGC
TCCTTCAGTGCAGACAACCTCACAGCCCCTGATGAGGACAGAGAGATGAACAACCTCCAG
CTGGCCCTGGCCCGCATCCAGAGGGGCCTGCGCTTTGTCAAGCGGACCACCTGGGATTTC
TGCTGTGGTCTCCTGCGGCACCGGCCTCAGAAGCCCGCAGCCCTTGCCGCCCAGGGCCAG
CTGCCCAGCTGCATTGCCACCCCCTACTCCCCGCCACCCCCAGAGACGGAGAAGGTGCCT
CCCACCCGCAAGGAAACACAGTTTGAGGAAGGCGAGCAACCAGGCCAGGGCACCCCCGGG
GATCCAGAGCCCGTGTGTGTGCCCATCGCTGTGGCCGAGTCAGACACAGATGACCAAGAA
GAGGATGAGGAGAACAGCCTGGGCACGGAGGAGGAGTCCAGCAAGCAGCAGGAATCCCAG
CCTGTGTCCGGCTGGCCCAGAGGCCCTCCGGATTCCAGGACCTGGAGCCAGGTGTCAGCG
ACTGCCTCCTCTGAGGCCGAGGCCAGTGCATCTCAGGCCGACTGGCGGCAGCAGTGGAAA
GCGGAACCCCAGGCCCCAGGGTGCGGTGAGACCCCAGAGGACAGTTGCTCCGAGGGCAGC
ACAGCAGACATGACCAACACCGCTGAGCTCCTGGAGCAGATCCCTGACCTCGGCCAGGAT
GTCAAGGACCCAGAGGACTGCTTCACTGAAGGCTGTGTCCGGCGCTGTCCCTGCTGTGCG
GTGGACACCACACAGGCCCCAGGGAAGGTCTGGTGGCGGTTGCGCAAGACCTGCTACCAC
ATCGTGGAGCACAGCTGGTTCGAGACATTCATCATCTTCATGATCCTACTCAGCAGTGGA
GCGCTGGCCTTCGAGGACATCTACCTAGAGGAGCGGAAGACCATCAAGGTTCTGCTTGAG
TATGCCGACAAGATGTTCACATATGTCTTCGTGCTGGAGATGCTGCTCAAGTGGGTGGCC
TACGGCTTCAAGAAGTACTTCACCAATGCCTGGTGCTGGCTCGACTTCCTCATCGTAGAC
GTCTCTCTGGTCAGCCTGGTGGCCAACACCCTGGGCTTTGCCGAGATGGGCCCCATCAAG
TCACTGCGGACGCTGCGTGCACTCCGTCCTCTGAGAGCTCTGTCACGATTTGAGGGCATG
AGGGTGGTGGTCAATGCCCTGGTGGGCGCCATCCCGTCCATCATGAACGTCCTCCTCGTC
TGCCTCATCTTCTGGCTCATCTTCAGCATCATGGGCGTGAACCTCTTTGCGGGGAAGTTT
GGGAGGTGCATCAACCAGACAGAGGGAGACTTGCCTTTGAACTACACCATCGTGAACAAC
AAGAGCCAGTGTGAGTCCTTGAACTTGACCGGAGAATTGTACTGGACCAAGGTGAAAGTC
AACTTTGACAACGTGGGGGCCGGGTACCTGGCCCTTCTGCAGGTGGCAACATTTAAAGGC
TGGATGGACATTATGTATGCAGCTGTGGACTCCAGGGGGTATGAAGAGCAGCCTCAGTGG
GAATACAACCTCTACATGTACATCTATTTTGTCATTTTCATCATCTTTGGGTCTTTCTTC
ACCCTGAACCTCTTTATTGGTGTCATCATTGACAACTTCAACCAACAGAAGAAAAAGTTA
GGGGGCCAGGACATCTTCATGACAGAGGAGCAGAAGAAGTACTACAATGCCATGAAGAAG
CTGGGCTCCAAGAAGCCCCAGAAGCCCATCCCACGGCCCCTGAACAAGTACCAGGGCTTC
ATATTCGACATTGTGACCAAGCAGGCCTTTGACGTCACCATCATGTTTCTGATCTGCTTG
AATATGGTGACCATGATGGTGGAGACAGATGACCAAAGTCCTGAGAAAATCAACATCTTG
GCCAAGATCAACCTGCTCTTTGTGGCCATCTTCACAGGCGAGTGTATTGTCAAGCTGGCT
GCCCTGCGCCACTACTACTTCACCAACAGCTGGAATATCTTCGACTTCGTGGTTGTCATC
CTCTCCATCGTGGGCACTGTGCTCTCGGACATCATCCAGAAGTACTTCTTCTCCCCGACG
CTCTTCCGAGTCATCCGCCTGGCCCGAATAGGCCGCATCCTCAGACTGATCCGAGGGGCC
AAGGGGATCCGCACGCTGCTCTTTGCCCTCATGATGTCCCTGCCTGCCCTCTTCAACATC
GGGCTGCTGCTCTTCCTCGTCATGTTCATCTACTCCATCTTTGGCATGGCCAACTTCGCT
TATGTCAAGTGGGAGGCTGGCATCGACGACATGTTCAACTTCCAGACCTTCGCCAACAGC
ATGCTGTGCCTCTTCCAGATCACCACGTCGGCCGGCTGGGATGGCCTCCTCAGCCCCATC
CTCAACACTGGGCCGCCCTACTGCGACCCCACTCTGCCCAACAGCAATGGCTCTCGGGGG
GACTGCGGGAGCCCAGCCGTGGGCATCCTCTTCTTCACCACCTACATCATCATCTCCTTC
CTCATCGTGGTCAACATGTACATTGCCATCATCCTGGAGAACTTCAGCGTGGCCACGGAG
GAGAGCACCGAGCCCCTGAGTGAGGACGACTTCGATATGTTCTATGAGATCTGGGAGAAA
TTTGACCCAGAGGCCACTCAGTTTATTGAGTATTCGGTCCTGTCTGACTTTGCCGACGCC
CTGTCTGAGCCACTCCGTATCGCCAAGCCCAACCAGATAAGCCTCATCAACATGGACCTG
CCCATGGTGAGTGGGGACCGCATCCATTGCATGGACATTCTCTTTGCCTTCACCAAAAGG
GTCCTGGGGGAGTCTGGGGAGATGGACGCCCTGAAGATCCAGATGGAGGAGAAGTTCATG
GCAGCCAACCCATCCAAGATCTCCTACGAGCCCATCACCACCACACTCCGGCGCAAGCAC
GAAGAGGTGTCGGCCATGGTTATCCAGAGAGCCTTCCGCAGGCACCTGCTGCAACGCTCT
TTGAAGCATGCCTCCTTCCTCTTCCGTCAGCAGGCGGGCAGCGGCCTCTCCGAAGAGGAT
GCCCCTGAGCGAGAGGGCCTCATCGCCTACGTGATGAGTGAGAACTTCTCCCGACCCCTT
GGCCCACCCTCCAGCTCCTCCATCTCCTCCACTTCCTTCCCACCCTCCTATGACAGTGTC
ACTAGAGCCACCAGCGATAACCTCCAGGTGCGGGGGTCTGACTACAGCCACAGTGAAGAT
CTCGCCGACTTCCCCCCTTCTCCGGACAGGGACCGTGAGTCCATCGTGTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
SCN5A  |
| Target 1 GenAtlas ID |
SCN5A  |
| Target 1 HGNC ID |
HGNC:10593  |
| Target 1 Chromosome Location |
3 |
| Target 1 Locus |
3p21 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, George AL Jr: Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation. 1999 Jun 22;99(24):3165-71. [PubMed
]
- Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH: Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. Am J Med Genet. 1999 Oct 29;86(5):470-6. [PubMed
]
- Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed
]
- Wehrens XH, Rossenbacker T, Jongbloed RJ, Gewillig M, Heidbuchel H, Doevendans PA, Vos MA, Wellens HJ, Kass RS: A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. Hum Mutat. 2003 May;21(5):552. [PubMed
]
- Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG: Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):554-8. [PubMed
]
- Bennett PB, Yazawa K, Makita N, George AL Jr: Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995 Aug 24;376(6542):683-5. [PubMed
]
- Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995 Mar 10;80(5):805-11. [PubMed
]
- Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MT: Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 Sep;4(9):1603-7. [PubMed
]
- Makita N, Shirai N, Nagashima M, Matsuoka R, Yamada Y, Tohse N, Kitabatake A: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Lett. 1998 Feb 13;423(1):5-9. [PubMed
]
- An RH, Wang XL, Kerem B, Benhorin J, Medina A, Goldmit M, Kass RS: Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits. Circ Res. 1998 Jul 27;83(2):141-6. [PubMed
]
|
| Target 1 Drug References |
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
706 |
| Target 2 Name |
Glutamate [NMDA] receptor subunit 3A |
| Target 2 Synonyms |
- Glutamate receptor subunit 3A precursor
- N-methyl-D-aspartate receptor subtype NR3A
- NMDAR-L
|
| Target 2 Gene Name |
GRIN3A |
| Target 2 Protein Sequence |
>Glutamate [NMDA] receptor subunit 3A precursor
MRRLSLWWLLSRVCLLLPPPCALVLAGVPSSSSHPQPCQILKRIGHAVRVGAVHLQPWTT
APRAASRAPDDSRAGAQRDEPEPGTRRSPAPSPGARWLGSTLHGRGPPGSRKPGEGARAE
ALWPRDALLFAVDNLNRVEGLLPYNLSLEVVMAIEAGLGDLPLLPFSSPSSPWSSDPFSF
LQSVCHTVVVQGVSALLAFPQSQGEMMELDLVSLVLHIPVISIVRHEFPRESQNPLHLQL
SLENSLSSDADVTVSILTMNNWYNFSLLLCQEDWNITDFLLLTQNNSKFHLGSIINITAN
LPSTQDLLSFLQIQLESIKNSTPTVVMFGCDMESIRRIFEITTQFGVMPPELRWVLGDSQ
NMEELRTEGLPLGLIAHGKTTQSVFEHYVQDAMELVARAVATATMIQPELALIPSTMNCM
EVETTNLTSGQYLSRFLANTTFRGLSGSIRVKGSTIVSSENNFFIWNLQHDPMGKPMWTR
LGSWQGRKIVMDYGIWPEQAQRHKTHFQHPSKLHLRVVTLIEHPFVFTREVDDEGLCPAG
QLCLDPMTNDSSTLDSLFSSLHSSNDTVPIKFKKCCYGYCIDLLEKIAEDMNFDFDLYIV
GDGKYGAWKNGHWTGLVGDLLRGTAHMAVTSFSINTARSQVIDFTSPFFSTSLGILVRTR
DTAAPIGAFMWPLHWTMWLGIFVALHITAVFLTLYEWKSPFGLTPKGRNRSKVFSFSSAL
NICYALLFGRTVAIKPPKCWTGRFLMNLWAIFCMFCLSTYTANLAAVMVGEKIYEELSGI
HDPKLHHPSQGFRFGTVRESSAEDYVRQSFPEMHEYMRRYNVPATPDGVEYLKNNPEKLD
AFIMDKALLDYEVSIDADCKLLTVGKPFAIEGYGIGLPPNSPLTANISELISQYKSHGFM
DMLHDKWYRVVPCGKRSFAVTETLQMGIKHFSGLFVLLCIGFGLSILTTIGEHIVYRLLL
PRIKNKSKLQYWLHTSQRLHRAINTSFIEEKQQHFKTKRVEKRSNVGPRQLTVWNTSNLS
HDNRRKYIFSDEEGQNQLGIRIHQDIPLPPRRRELPALRTTNGKADSLNVSRNSVMQELS
ELEKQIQVIRQELQLAVSRKTELEEYQRTSRTCES
|
| Target 2 Number of Residues |
1133 |
| Target 2 Molecular Weight |
125597 |
| Target 2 Theoretical pI |
7.81 |
| Target 2 GO Classification |
|
Function
|
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
excitatory extracellular ligand-gated ion channel activity
glutamate-gated ion channel activity
signal transducer activity
receptor activity
transmembrane receptor activity
glutamate receptor activity
ionotropic glutamate receptor activity |
|
Process
|
physiological process
cellular physiological process
transport
ion transport |
|
Component
|
cell
membrane |
|
| Target 2 General Function |
Involved in ionotropic glutamate receptor activity |
| Target 2 Specific Function |
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism |
| Target 2 Pathways |
Not Available
|
| Target 2 Reactions |
Not Available |
| Target 2 Pfam Domain Function |
|
| Target 2 Signals |
|
| Target 2 Transmembrane Regions |
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
20372905  |
| Target 2 UniProtKB/Swiss-Prot ID |
Q8TCU5  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
NMD3A_HUMAN  |
| Target 2 PDB ID |
Not Available |
| Target 2 Cellular Location |
- Cell membrane
- multi-pass membrane protein. Enriched in post-synaptic plasma membrane and post-synap
|
| Target 2 Gene Sequence |
>3348 bp
ATGAGGAGACTGAGTTTGTGGTGGCTGCTGAGCAGGGTCTGTCTGCTGTTGCCGCCGCCC
TGCGCACTGGTGCTGGCCGGGGTGCCCAGCTCCTCCTCGCACCCGCAGCCCTGCCAGATC
CTCAAGCGCATCGGGCACGCGGTGAGGGTGGGCGCGGTGCACTTGCAGCCCTGGACCACC
GCCCCCCGCGCGGCCAGCCGCGCTCCGGACGACAGCCGAGCAGGAGCCCAGAGGGATGAG
CCGGAGCCAGGGACTAGGCGGTCCCCGGCGCCCTCGCCGGGCGCACGCTGGTTGGGGAGC
ACCCTGCATGGCCGGGGGCCGCCGGGCTCCCGTAAGCCCGGGGAGGGCGCCAGGGCGGAG
GCCCTGTGGCCACGGGACGCCCTCCTATTTGCCGTGGACAACCTGAACCGCGTGGAAGGG
CTGCTACCCTACAACCTGTCTTTGGAAGTAGTGATGGCCATCGAGGCAGGCCTGGGCGAT
CTGCCACTTTTGCCCTTCTCCTCCCCTAGTTCGCCATGGAGCAGTGACCCTTTCTCCTTC
CTGCAAAGTGTGTGCCATACCGTGGTGGTGCAAGGGGTGTCGGCGCTGCTCGCCTTCCCC
CAGAGCCAGGGCGAAATGATGGAGCTCGACTTGGTCAGCTTAGTCCTGCACATTCCAGTG
ATCAGCATCGTGCGCCACGAGTTTCCGCGGGAGAGTCAGAATCCCCTTCACCTACAACTG
AGTTTAGAAAATTCATTAAGTTCTGATGCTGATGTCACTGTCTCAATCCTGACCATGAAC
AACTGGTACAATTTTAGCTTGTTGCTGTGCCAGGAAGACTGGAACATCACCGACTTCCTC
CTCCTTACCCAGAATAATTCCAAGTTCCACCTTGGTTCTATCATCAACATCACCGCTAAC
CTCCCCTCCACCCAGGACCTCTTGAGCTTCCTACAGATCCAGCTTGAGAGTATTAAGAAC
AGCACACCCACAGTGGTGATGTTTGGCTGCGACATGGAAAGTATCCGGCGGATTTTCGAA
ATTACAACCCAGTTTGGGGTCATGCCCCCTGAACTTCGTTGGGTGCTGGGAGATTCCCAG
AATATGGAGGAACTGAGGACAGAGGGTCTGCCCTTAGGACTCATTGCTCATGGAAAAACA
ACACAGTCTGTCTTTGAGCACTACGTACAAGATGCTATGGAGCTGGTCGCAAGAGCTGTA
GCCACAGCCACCATGATCCAACCAGAACTTGCTCTCATTCCCAGCACGATGAACTGCATG
GAGGTGGAAACTACAAATCTCACTTCAGGACAATATTTATCAAGGTTTCTAGCCAATACC
ACTTTCAGAGGCCTCAGTGGTTCCATCAGAGTAAAAGGTTCCACCATCGTCAGCTCAGAA
AACAACTTTTTCATCTGGAATCTTCAACATGACCCCATGGGAAAGCCAATGTGGACCCGC
TTGGGCAGCTGGCAGGGGAGAAAGATTGTCATGGACTATGGAATATGGCCAGAGCAGGCC
CAGAGACACAAAACCCACTTCCAACATCCAAGTAAGCTACACTTGAGAGTGGTTACCCTG
ATTGAGCATCCTTTTGTCTTCACAAGGGAGGTAGATGATGAAGGCTTGTGCCCTGCTGGC
CAACTCTGTCTAGACCCCATGACTAATGACTCTTCCACACTGGACAGCCTTTTTAGCAGC
CTCCATAGCAGTAATGATACAGTGCCCATTAAATTCAAGAAGTGCTGCTATGGATATTGC
ATTGATCTGCTGGAAAAGATAGCAGAAGACATGAACTTTGACTTCGACCTCTATATTGTA
GGGGATGGAAAGTATGGAGCCTGGAAAAATGGGCACTGGACTGGGCTAGTGGGTGATCTC
CTGAGAGGGACTGCCCACATGGCAGTCACTTCCTTTAGCATCAATACTGCACGGAGCCAG
GTGATAGATTTCACCAGCCCTTTCTTCTCCACCAGCTTGGGCATCTTAGTGAGGACCCGA
GATACAGCAGCTCCCATTGGAGCCTTCATGTGGCCACTCCACTGGACAATGTGGCTGGGG
ATTTTTGTGGCTCTGCACATCACTGCCGTCTTCCTCACTCTGTATGAATGGAAGAGTCCA
TTTGGTTTGACTCCCAAGGGGCGAAATAGAAGTAAAGTCTTCTCCTTTTCTTCAGCCTTG
AACATCTGTTATGCCCTCTTGTTTGGCAGAACAGTGGCCATCAAACCTCCAAAATGTTGG
ACTGGAAGGTTTCTAATGAACCTTTGGGCCATTTTCTGTATGTTTTGCCTTTCCACATAC
ACGGCAAACTTGGCTGCTGTCATGGTAGGTGAGAAGATCTATGAAGAGCTTTCTGGAATA
CATGACCCCAAGTTACATCATCCTTCCCAAGGATTCCGCTTTGGAACTGTCCGAGAAAGC
AGTGCTGAAGATTATGTGAGACAAAGTTTCCCAGAGATGCATGAATATATGAGAAGGTAC
AATGTTCCAGCCACCCCTGATGGAGTGGAGTATCTGAAGAACAATCCAGAGAAACTAGAC
GCCTTCATCATGGACAAAGCCCTTCTGGATTATGAAGTGTCAATAGATGCTGACTGCAAA
CTTCTCACTGTGGGGAAGCCATTTGCCATAGAAGGATACGGCATTGGCCTCCCACCCAAC
TCTCCATTGACCGCCAACATATCCGAGCTAATCAGTCAATACAAGTCACATGGGTTTATG
GATATGCTCCATGACAAGTGGTACAGGGTGGTTCCCTGTGGCAAGAGAAGTTTTGCTGTC
ACGGAGACTTTGCAAATGGGCATCAAACACTTCTCTGGGCTCTTTGTGCTGCTGTGCATT
GGATTTGGTCTGTCCATTTTGACCACCATTGGTGAGCACATAGTATACAGGCTGCTGCTA
CCACGAATCAAAAACAAATCCAAGCTGCAATACTGGCTCCACACCAGCCAGAGATTACAC
AGAGCAATAAATACATCATTTATAGAGGAAAAGCAGCAGCATTTCAAGACCAAACGTGTG
GAAAAGAGGTCTAATGTGGGACCCCGTCAGCTTACCGTATGGAATACTTCCAATCTGAGT
CATGACAACCGACGGAAATACATCTTTAGTGATGAGGAAGGACAAAACCAGCTGGGCATC
CGGATCCACCAGGACATCCCCCTCCCTCCAAGGAGAAGAGAGCTCCCTGCCTTGCGGACC
ACCAATGGGAAAGCAGACTCCCTAAATGTATCTCGGAACTCAGTGATGCAGGAACTCTCA
GAGCTCGAGAAGCAGATTCAGGTGATCCGTCAGGAGCTGCAGCTGGCTGTGAGCAGGAAA
ACGGAGCTGGAGGAGTATCAAAGGACAAGTCGGACTTGTGAGTCCTAG
|
| Target 2 GenBank Gene ID |
|
| Target 2 GeneCard ID |
GRIN3A  |
| Target 2 GenAtlas ID |
GRIN3A  |
| Target 2 HGNC ID |
HGNC:16767  |
| Target 2 Chromosome Location |
9 |
| Target 2 Locus |
9q31.1 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- Andersson O, Stenqvist A, Attersand A, von Euler G: Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Genomics. 2001 Dec;78(3):178-84. [PubMed
]
- Nagase T, Kikuno R, Ohara O: Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. DNA Res. 2001 Dec 31;8(6):319-27. [PubMed
]
- Eriksson M, Nilsson A, Froelich-Fabre S, Akesson E, Dunker J, Seiger A, Folkesson R, Benedikz E, Sundstrom E: Cloning and expression of the human N-methyl-D-aspartate receptor subunit NR3A. Neurosci Lett. 2002 Mar 22;321(3):177-81. [PubMed
]
|
| Target 2 Drug References |
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed
]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed
]
|