Lamotrigine (T3D2570)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (10)XML
Targets (10)
Record Information
Version2.0
Creation Date2009-07-05 03:30:53 UTC
Update Date2014-12-24 20:25:43 UTC
Accession NumberT3D2570
Identification
Common NameLamotrigine
ClassSmall Molecule
DescriptionLamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. It is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring. The exact way lamotrigine works is unknown.
Compound Type
  • Amine
  • Analgesic
  • Anticonvulsant
  • Antidepressant
  • Antidepressive Agent
  • Antimanic Agent
  • Calcium Channel Blocker
  • Drug
  • Excitatory Amino Acid Antagonist
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
3,5-Diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine
Convulsan
Crisomet
Dafex
Daksol
Danoptin
Dezepil
Elmendos
Epilepax
Epimil
Epiral
Epitec
Epitrigine
GW 273293
Labileno
Lambipol
Lamect
Lameptil
Lameptil S
Lametec
Lamez
Lamictal
Lamictal CD
Lamictal XR
Lamictin
Lamotrigina
Lamotriginum
Lamotrix
Larig
Medotrigin
Mogine
Trimolep
Trogine
Xebarin
Chemical FormulaC9H7Cl2N5
Average Molecular Mass256.091 g/mol
Monoisotopic Mass255.008 g/mol
CAS Registry Number84057-84-1
IUPAC Name6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
Traditional Namelamotrigine
SMILESNC1=C(N=NC(=N)N1)C1=C(Cl)C(Cl)=CC=C1
InChI IdentifierInChI=1S/C9H7Cl2N5/c10-5-3-1-2-4(6(5)11)7-8(12)14-9(13)16-15-7/h1-3H,(H4,12,13,14,16)
InChI KeyInChIKey=PYZRQGJRPPTADH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dichlorobenzenes. Dichlorobenzenes are compounds containing a benzene with exactly two chlorine atoms attached to it.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentDichlorobenzenes
Alternative Parents
Substituents
  • 1,2-dichlorobenzene
  • Aminotriazine
  • Aryl chloride
  • Aryl halide
  • Triazine
  • Imidolactam
  • 1,2,4-triazine
  • Heteroaromatic compound
  • Organoheterocyclic compound
  • Azacycle
  • Amine
  • Primary amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite to pale cream-colored powder. Crystals from isopropanol (7).
Experimental Properties
PropertyValue
Melting Point216-218°C (uncorr)
Boiling PointNot Available
Solubility4.88e-01 g/L
LogP2.5
Predicted Properties
PropertyValueSource
Water Solubility0.49 g/LALOGPS
logP1.87ALOGPS
logP1.93ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)14.98ChemAxon
pKa (Strongest Basic)5.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area90.71 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity66.62 m³·mol⁻¹ChemAxon
Polarizability23.1 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-1890000000-760d1195ef5ceae750262017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-2940000000-1a4f3a098b426ac4febb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0090000000-0ca7be847ef73a25032b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0c09-0890000000-f7244245bf6816d03dc72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-97d10d3ad5d45edcaeba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-b2dbf89c13423bc1b59f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-d26cb5886894916aa1d82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0590000000-528845465e0a140f6b602017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0930000000-9a68c83a3573a48cf6c22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0kmi-0900000000-bb97e1aecda1747cbf292017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-97d10d3ad5d45edcaeba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-97d10d3ad5d45edcaeba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0090000000-1e756e80b9a7d4b0dd182017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0490000000-a29a09ef58e19c7e62e12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0940000000-85279d67921a0106c4e22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0kmi-0900000000-eba38744d927d1c39a742017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0ab9-0790000000-036c53ed1835e3d333482017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0290000000-26664a56093e292ec5512017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0190000000-33187897c9fb0b0a178f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-2940000000-1a4f3a098b426ac4febb2017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0090000000-4283661a0ad9c11f2e422016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0090000000-7f7abcbaad5c89ee81092016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01w0-2490000000-3dbf5856c09bbcdde1842016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-55f38f4a1708215a25092016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ug0-0090000000-067db3f005caf26c9b9a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9010000000-87e51d16bdb0c8facd592016-08-03View Spectrum
Toxicity Profile
Route of ExposureInhalation (1); dermal (1); ingestion (1).
Mechanism of ToxicityOne proposed mechanism of action of Lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. in vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels and/or calcium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Studies on lamotrigine show binding to sodium channels similar to local anesthetics.
MetabolismLamotrigine is metabolized predominantly by glucuronic acid conjugation. The major metabolite is an inactive 2-N-glucuronide conjugate. Exretion occur in the urine and the feces with unchanged lamotrigine (10%), the 2-N-glucuronide (76%), a 5-N-glucuronide (10%), a 2-N-methyl metabolite (0.14%), and other unidentified minor metabolites (4%). (1) Half Life: 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)
Toxicity ValuesLD50: 250 (mg/kg) (mice) LD50: 250 (mg/kg) (rat) LD50> 640 (mg/kg) (oral, rat) (Sawyer) LD50> 640 (mg/kg) (oral, mice) (Sawyer)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression. Off-label uses include the treatment of peripheral neuropathy, trigeminal neuralgia, cluster headaches, migraines, and reducing neuropathic pain. (1, 8)
Minimum Risk LevelNot Available
Health EffectsSerious skin rashes, acute multiorgan failure, blood dyscrasias, sudden unexplained death in epilepsy, withdrawal seizures. (1) May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs.
TreatmentThere are no specific antidotes for lamotrigine. Following a suspected overdose, hospitalization of the patient is advised. General supportive care is indicated, including frequent monitoring of vital signs and close observation of the patient. If indicated, emesis should be induced or gastric lavage should be performed; usual precautions should be taken to protect the airway. (1)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00555
HMDB IDHMDB14695
PubChem Compound ID3878
ChEMBL IDCHEMBL741
ChemSpider ID3741
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID6367
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLamotrigine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLamotrigine
References
Synthesis Reference

Grahame Roy Lee, “Process for the preparation of lamotrigine.” U.S. Patent US5925755, issued January, 1981.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Backonja M: Neuromodulating drugs for the symptomatic treatment of neuropathic pain. Curr Pain Headache Rep. 2004 Jun;8(3):212-6. [15115640 ]
  3. Barbosa L, Berk M, Vorster M: A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry. 2003 Apr;64(4):403-7. [12716240 ]
  4. Jensen TS: Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6 Suppl A:61-8. [11888243 ]
  5. Pappagallo M: Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and migraine. Clin Ther. 2003 Oct;25(10):2506-38. [14667954 ]
  6. Tehrani SP, Daryaafzoon M, Bakhtiarian A, Ejtemaeemehr S, Sahraei H: The effects of lamotrigine on the acquisition and expression of morphine-induced place preference in mice. Pak J Biol Sci. 2009 Jan 1;12(1):33-9. [19579915 ]
  7. O'Neil MJ (ed) (2001). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc.
  8. Wikipedia. Lamotrigine. Last Updated 25 July 2009. [Link]
  9. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Sodium channel protein type 2 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
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.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5010 uMNot AvailableBindingDB 50031299
IC50>100 uMNot AvailableBindingDB 50031299
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
  4. Drizin I, Gregg RJ, Scanio MJ, Shi L, Gross MF, Atkinson RN, Thomas JB, Johnson MS, Carroll WA, Marron BE, Chapman ML, Liu D, Krambis MJ, Shieh CC, Zhang X, Hernandez G, Gauvin DM, Mikusa JP, Zhu CZ, Joshi S, Honore P, Marsh KC, Roeloffs R, Werness S, Krafte DS, Jarvis MF, Faltynek CR, Kort ME: Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain. Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. doi: 10.1016/j.bmc.2008.05.003. Epub 2008 May 6. [18501613 ]
  5. Fantini M, Rivara M, Zuliani V, Kalmar CL, Vacondio F, Silva C, Baheti AR, Singh N, Merrick EC, Katari RS, Cocconcelli G, Ghiron C, Patel MK: 2,4(5)-diarylimidazoles as inhibitors of hNaV1.2 sodium channels: pharmacological evaluation and structure-property relationships. Bioorg Med Chem. 2009 May 15;17(10):3642-8. doi: 10.1016/j.bmc.2009.03.067. Epub 2009 Apr 10. [19394229 ]
Target Details
2. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
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. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5062 uMNot AvailableBindingDB 50031299
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
  4. Drizin I, Gregg RJ, Scanio MJ, Shi L, Gross MF, Atkinson RN, Thomas JB, Johnson MS, Carroll WA, Marron BE, Chapman ML, Liu D, Krambis MJ, Shieh CC, Zhang X, Hernandez G, Gauvin DM, Mikusa JP, Zhu CZ, Joshi S, Honore P, Marsh KC, Roeloffs R, Werness S, Krafte DS, Jarvis MF, Faltynek CR, Kort ME: Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain. Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. doi: 10.1016/j.bmc.2008.05.003. Epub 2008 May 6. [18501613 ]
Target Details
3. Sodium channel protein type 1 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
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.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
Target Details
4. Sodium channel protein type 3 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
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.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
Target Details
5. Sodium channel protein type 4 subunit alpha
General Function:
Voltage-gated sodium channel activity
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. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory17 uMNot AvailableBindingDB 50031299
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Lipkind GM, Fozzard HA: Molecular modeling of local anesthetic drug binding by voltage-gated sodium channels. Mol Pharmacol. 2005 Dec;68(6):1611-22. Epub 2005 Sep 20. [16174788 ]
  3. Yang J, Gharagozloo P, Yao J, Ilyin VI, Carter RB, Nguyen P, Robledo S, Woodward RM, Hogenkamp DJ: 3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers. J Med Chem. 2004 Mar 11;47(6):1547-52. [14998340 ]
Target Details
6. Sodium channel protein type 8 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
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. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
Gene Name:
SCN8A
Uniprot ID:
Q9UQD0
Molecular Weight:
225278.005 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
Target Details
7. Sodium channel protein type 9 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
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. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. 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. [17016423 ]
Target Details
8. Dihydrofolate reductase
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
9. Potassium voltage-gated channel subfamily H member 2
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50229.08677 uMNot AvailableBindingDB 50031299
References
  1. Coi A, Massarelli I, Testai L, Calderone V, Bianucci AM: Identification of "toxicophoric" features for predicting drug-induced QT interval prolongation. Eur J Med Chem. 2008 Nov;43(11):2479-88. doi: 10.1016/j.ejmech.2007.12.025. Epub 2008 Jan 5. [18262683 ]
Target Details
10. Sodium channel protein type 10 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Tetrodotoxin-resistant channel that 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 sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5096 uMNot AvailableBindingDB 50031299
References
  1. Drizin I, Gregg RJ, Scanio MJ, Shi L, Gross MF, Atkinson RN, Thomas JB, Johnson MS, Carroll WA, Marron BE, Chapman ML, Liu D, Krambis MJ, Shieh CC, Zhang X, Hernandez G, Gauvin DM, Mikusa JP, Zhu CZ, Joshi S, Honore P, Marsh KC, Roeloffs R, Werness S, Krafte DS, Jarvis MF, Faltynek CR, Kort ME: Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain. Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. doi: 10.1016/j.bmc.2008.05.003. Epub 2008 May 6. [18501613 ]