Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDC00255

Target Information
NameSodium-dependent serotonin transporter    
Type of targetClinical trial target    
Synonyms5HT transporter    
5HTT    
Solute carrier family 6 member 4    
DiseaseSchizophrenia
[ICD9: 295   ICD10: F20]
[1]
Drug(s)VilazodonePhase III completedMajor Depressive Disorder[2]
LY367265DiscontinuedDepression[2]
SLV-310Suspended in Phase IISchizophrenia[1]
YM-992Discontinued in Phase IIDepression[2]
UniProt IDP31645
FunctionTerminates the action of serotonin by its high affinity sodium-dependent reuptake into presynaptic terminals.    
SequenceMETTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT PGTFKERIIKSITPETPTEIPCGDIRLNAV//
Target ValidationClick to Find Target Validation Information.    
Inhibitor (+/-)-nantenine[3]
(2R,3R)-iodoreboxetine[4]
(2S,3S)-iodoreboxetine[4]
(R)-DULOXETINE[5]
(R)-Norfluoxetine[6]
(S)-NORDULOXETINE[7]
(S)-Norfluoxetine[6]
(S,S)-reboxetine[8]
1- (1,2-diphenylethyl)piperazine[9]
1- (1,3-diphenylpropyl)piperazine[10]
1- (1,4-diphenylbutan-2-yl)piperazine[10]
1-benzylpiperidine hydrochloride[11]
10R-hydroxylobel-7-ene[12]
10R-hydroxylobelane[12]
10S-hydroxylobel-7-ene[12]
10S-hydroxylobelane[12]
1S,2R-milnacipran[13]
6-nitroquipazine[14]
8R-hydroxylobel-9-ene[15]
8R-hydroxylobelane[12]
8S-hydroxylobel-9-ene[12]
8S-hydroxylobelane[12]
A-80426[16]
COCAINE.HCL[11]
D-166A[17]
D-211A[17]
D-211B[17]
D-254C[17]
D-257A[17]
D-257C[17]
DIFLUOROBENZTROPINE[18]
ESCITALOPRAM OXALATE[19]
FLUOXETINE HYDROCHLORIDE[20]
GBR-12909[21]
Irindalone[22]
JNJ-28583867[23]
KF-A5[24]
KF-A6[24]
LITOXETINE[25]
LY367265[2]
MDL-28618[26]
METHYLENEDIOXYAMPHETAMINE[27]
METHYLENEDIOXYMETHAMPHETAMINE[27]
NISOXETINE[5]
O-DESMETHYL TRAMADOL[28]
PF-18298,   PF-184298[29]
PF-3409409[30]
PF-526014[29]
PYROVALERONE[31]
QUIPAZINE[32]
R-226161[33]
R-NORDULOXETINE[7]
RTI-219[34]
S-34324[35]
S33005[2]
TEFLUDAZINE[36]
Vilazodone[2]
WIN-35065[34]
WIN-35065-2[37]
WIN-35066-2[38]
WIN_35428[37]
YM-992[2]
ZIMELIDINE[39]
para-Methoxyamphetamine[27]
para-chloroamphetamine[27]
Antagonist4-Methoxyamphetamine[40]
BlockerSLV-310[1]
ModulatorMMDA[41]
MultitargetSLV-310[1]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. To Reference
Ref 2Curr Top Med Chem. 2006;6(17):1801-23.Serotonin reuptake inhibitors: the corner stone in treatment of depression for half a century--a medicinal chemistry survey. To Reference
Ref 3Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference
Ref 4Bioorg Med Chem Lett. 2008 Sep 15;18(18):4940-3. Epub 2008 Aug 19.New iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter. To Reference
Ref 5Bioorg Med Chem Lett. 2009 Jan 1;19(1):58-61. Epub 2008 Nov 13.1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors. To Reference
Ref 6Bioorg Med Chem. 2009 Jan 1;17(1):337-43. Epub 2008 Nov 5.Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression. To Reference
Ref 7Bioorg Med Chem. 2009 Oct 1;17(19):6890-7. Epub 2009 Aug 20.Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression. To Reference
Ref 8J Med Chem. 2009 Jan 8;52(1):62-73.Synthesis, radiosynthesis, and biological evaluation of carbon-11 and fluorine-18 labeled reboxetine analogues: potential positron emission tomography radioligands for in vivo imaging of the norepinephrine transporter. To Reference
Ref 9Bioorg Med Chem Lett. 2006 Aug 15;16(16):4345-8. Epub 2006 Jun 5.N-(1,2-diphenylethyl)piperazines: a new class of dual serotonin/noradrenaline reuptake inhibitor. To Reference
Ref 10Bioorg Med Chem Lett. 2006 Aug 15;16(16):4349-53. Epub 2006 Jun 5.Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors. To Reference
Ref 11J Med Chem. 2007 May 31;50(11):2718-31. Epub 2007 May 10.Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate. To Reference
Ref 12Bioorg Med Chem Lett. 2006 Oct 1;16(19):5018-21. Epub 2006 Aug 14.Des-keto lobeline analogs with increased potency and selectivity at dopamine and serotonin transporters. To Reference
Ref 13J Med Chem. 2008 Nov 27;51(22):7265-72.Characterization of thien-2-yl 1S,2R-milnacipran analogues as potent norepinephrine/serotonin transporter inhibitors for the treatment of neuropathic pain. To Reference
Ref 14Bioorg Med Chem. 2007 May 15;15(10):3499-504. Epub 2007 Mar 3.Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 5: 2'-Substituted 6-nitroquipazines. To Reference
Ref 15Bioorg Med Chem. 2010 Jan 15;18(2):640-9. Epub 2009 Dec 6.Lobeline esters as novel ligands for neuronal nicotinic acetylcholine receptors and neurotransmitter transporters. To Reference
Ref 16J Med Chem. 1997 Mar 28;40(7):1049-62.Structure-activity studies for a novel series of N-(arylethyl)-N-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamine s possessing dual 5-HT uptake inhibiting and alpha2-antagonistic activities. To Reference
Ref 17Bioorg Med Chem. 2008 Mar 15;16(6):2769-78. Epub 2008 Jan 11.Further structural optimization of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine and 1,4-diazabicyclo[3.3.1]nonane derivatives by introducing an exocyclic hydroxyl group: interaction with dopamine, serotonin, and norepinephrine transporters. To Reference
Ref 18J Med Chem. 2006 Oct 19;49(21):6391-9.Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation. To Reference
Ref 19J Med Chem. 2010 Aug 12;53(15):5549-57.Synthesis, fluorine-18 radiolabeling, and biological evaluation of N-((E)-4-fluorobut-2-en-1-yl)-2beta-carbomethoxy-3beta-(4'-halophenyl)nortropanes: candidate radioligands for in vivo imaging of the brain dopamine transporter with positron emission tomography. To Reference
Ref 20Bioorg Med Chem. 2010 Dec 1;18(23):8356-64. Epub 2010 Sep 29.Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. To Reference
Ref 21Bioorg Med Chem Lett. 2008 Oct 1;18(19):5238-41. Epub 2008 Aug 22.Dual DAT/sigma1 receptor ligands based on 3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol. To Reference
Ref 22J Med Chem. 1988 Dec;31(12):2247-56.Antihypertensive activity in a series of 1-piperazino-3-phenylindans with potent 5-HT2-antagonistic activity. To Reference
Ref 23Bioorg Med Chem Lett. 2008 Jan 1;18(1):39-43. Epub 2007 Nov 13.Synthesis and biological activity of piperazine and diazepane amides that are histamine H3 antagonists and serotonin reuptake inhibitors. To Reference
Ref 24Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40. Epub 2007 Sep 10.Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. To Reference
Ref 25Bioorg Med Chem Lett. 2009 Oct 15;19(20):5893-7. Epub 2009 Aug 21.Design and optimisation of selective serotonin re-uptake inhibitors with high synthetic accessibility: part 2. To Reference
Ref 26Bioorg Med Chem Lett. 2008 Aug 15;18(16):4495-8. Epub 2008 Jul 17.Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint. To Reference
Ref 27Eur J Med Chem. 2009 Dec;44(12):4862-88. Epub 2009 Aug 6.Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents. To Reference
Ref 28Bioorg Med Chem Lett. 2006 Feb;16(3):691-4. Epub 2005 Oct 27.Derivatives of tramadol for increased duration of effect. To Reference
Ref 29Bioorg Med Chem Lett. 2010 Jun 15;20(12):3788-92. Epub 2010 Apr 18.Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reducing ion channel activity. To Reference
Ref 30Bioorg Med Chem Lett. 2009 Aug 15;19(16):4579-83. Epub 2009 Jul 2.Design, synthesis and evaluation of N-[(3S)-pyrrolidin-3-yl]benzamides as selective noradrenaline reuptake inhibitors: CNS penetration in a more polar template. To Reference
Ref 31J Med Chem. 2006 Feb 23;49(4):1420-32.1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. To Reference
Ref 32Bioorg Med Chem Lett. 2000 Jul 17;10(14):1559-62.Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 1. To Reference
Ref 33Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 34J Med Chem. 2007 Jul 26;50(15):3686-95. Epub 2007 Jun 30.Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes. To Reference
Ref 35J Med Chem. 2005 Mar 24;48(6):2054-71.Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity. To Reference
Ref 36J Med Chem. 1983 Jul;26(7):935-47.Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans. To Reference
Ref 37J Med Chem. 1996 Oct 11;39(21):4139-41.3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: novel ligands with high affinity and selectivity at the dopamine transporter. To Reference
Ref 38J Med Chem. 2004 Dec 2;47(25):6401-9.Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers. To Reference
Ref 39J Med Chem. 1984 Nov;27(11):1508-15.Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralins. To Reference
Ref 40Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F: Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Aug;24(6):955-77. To Reference
Ref 41Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

   
 
 
Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links

 

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543