| + |
PRKG1 | up-regulates 
phosphorylation
|
SLC6A4 |
0.391 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158186 |
Thr276 |
SIWKGVKtSGKVVWV |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17913921 |
These results are consistent with the hypothesis that pkg phosphorylates hsert at thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by tm5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SRC | up-regulates quantity by stabilization
phosphorylation
|
SLC6A4 |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276386 |
Tyr142 |
MELALGQyHRNGCIS |
Rattus norvegicus |
Blood Platelet |
| pmid |
sentence |
| 21992875 |
We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276385 |
Tyr47 |
SGQISNGySAVPSPG |
Rattus norvegicus |
Blood Platelet |
| pmid |
sentence |
| 21992875 |
We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT. |
|
| Publications: |
2 |
Organism: |
Rattus Norvegicus |
| + |
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile | down-regulates activity 
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257794 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18487050 |
For [3H]paroxetine, [3H]citalopram, [3H]nisoxetine, and [3H]WIN35,428 the following KD values were obtained on the human monoamine transporters hSERT, hNET, and hDAT by homologous competition experiments: 0.69 nM [3H]paroxetine, 4.46 nM [3H]citalopram, 6.77 nM [3H]nisoxetine, and 24.1 [3H]WIN35,428. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
fluoxetine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258738 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
dothiepin | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258877 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
doxepin | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258879 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SLC6A4 | up-regulates quantity
relocalization
|
serotonin |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263953 |
|
|
Homo sapiens |
Central Nervous System |
| pmid |
sentence |
| 16789923 |
The function of the serotonin transporter (SERT) is to take up and release serotonin (5-hydroxytyptamine (5-HT)) from cells and this function of SERT in the central nervous system (CNS) is well-documented; SERT is the target of selective serotonin reuptake inhibitors used in the treatment of CNS disorders, such as depression. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263952 |
|
|
Homo sapiens |
Blood Platelet |
| pmid |
sentence |
| 17506858 |
Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
levomilnacipran | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257943 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18468895 |
Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
2-[[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethanamine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258880 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Norzotepine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257830 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 20223878 |
These results collectively demonstrate that norZTP exerts more potent inhibitory action than ZTP on norepinephrine transporters both in vitro and in vivo, presumably accounting for its antidepressant-like effect and low EPS propensity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
zotepine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257829 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20223878 |
These results collectively demonstrate that norZTP exerts more potent inhibitory action than ZTP on norepinephrine transporters both in vitro and in vivo, presumably accounting for its antidepressant-like effect and low EPS propensity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
lofepramine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258882 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
trimipramine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258741 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
atomoxetine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259067 |
|
|
in vitro |
|
| pmid |
sentence |
| 9871604 |
The gamma-amino alcohol/ether unit contained in venlafaxine, 2 fluoxetine, 3 and tomoxetine 3 has been prepared by a sequence of nitrile aldol reaction and nitrile reduction. Equilibrium dissociation constants KD for binding of (_+)-2 and (_+)-3 to hSERT, hNET, and hDAT are given in Table 2. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
(S)-duloxetine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257776 |
|
|
in vitro |
|
| pmid |
sentence |
| 18387300 |
Selective inhibition of serotonin (5-HT) and noradrenaline (NA) reuptake (SNRI) has been shown to be an attractive dual pharmacology approach for the treatment of a number of diseases.1,2 For example, dual 5- HT/NA reuptake inhibitor duloxetine (1) has shown clinical efficacy in the treatment of depression, pain, and urinary incontinence. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
nefazodone | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259068 |
|
|
in vitro |
|
| pmid |
sentence |
| 9871604 |
Equilibrium dissociation constants KD for binding of (_+)-2 and (_+)-3 to hSERT, hNET, and hDAT are given in Table 2. Nefazodone has similar affinities at hSERT, hNET, and hDAT, but has low potency |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
clomipramine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258876 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
venlafaxine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257836 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20378347 |
The cycloalkanol ethylamine scaffold was successfully utilized in the discovery and development of dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitors (SNRIs).1 Drugs such as venlafaxine (1) and duloxetine (2) possessing norepinephrine reuptake inhibition, either selectively or in combination with serotonin reuptake inhibition were approved for major depressive disorder (MDD). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
paroxetine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258739 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257795 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18487050 |
For [3H]paroxetine, [3H]citalopram, [3H]nisoxetine, and [3H]WIN35,428 the following KD values were obtained on the human monoamine transporters hSERT, hNET, and hDAT by homologous competition experiments: 0.69 nM [3H]paroxetine, 4.46 nM [3H]citalopram, 6.77 nM [3H]nisoxetine, and 24.1 [3H]WIN35,428. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
desipramine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258679 |
|
|
in vitro |
|
| pmid |
sentence |
| 9400006 |
In the SERT, the TCAs amitriptyline, nortriptyline, imipramine, desipramine and chloroimipramine were 4.5 to 10 times more potent (table 3) at the human SERT.in the SERT, the TCAs amitriptyline, nortriptyline, imipramine, desipramine and chloroimipramine were 4.5 to 10 times more potent (table 3) at the human SERT.Thus, amitriptyline, imipramine, nortriptyline and desipramine showed high affinity for the SERT, particularly the human version, and for the NET in which the secondary amines were more potent. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
protriptyline | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258737 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Phenelzine | down-regulates activity
chemical inhibition
|
SLC6A4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258744 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 9537821 |
Among the antidepressants that we tested, paroxetine, which is a serotonin selective re-uptake inhibitor based on animal data, was the most potent for the human serotonin transporter with a KD=0.13±0.01 nM. Some tricyclic antidepressants (clomipramine, imipramine and amitriptyline), as well as some other antidepressants (sertraline, fluoxetine, citalopram and fluvoxamine) and some of their metabolites (norfluoxetine, desmethylsertraline and desmethylcitalopram) were also very potent at the human serotonin transporter. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
SLC6A4
- 
- 