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NET

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Target not currently curated in GtoImmuPdb

Target id: 926

Nomenclature: NET

Systematic Nomenclature: SLC6A2

Family: Monoamine transporter subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 617 16q12.2 SLC6A2 solute carrier family 6 member 2
Mouse 12 617 8 44.99 cM Slc6a2 solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2
Rat - - 19p11 Slc6a2 solute carrier family 6 member 2
Previous and Unofficial Names Click here for help
NAT1 | NET1 | SLC6A5 | NaCl-dependent norepinephrine transporter | norepinephrine transporter | sodium-dependent noradrenaline transporter | NE transporter | solute carrier family 6 (neurotransmitter transporter), member 2 | solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 | solute carrier family 6 (neurotransmitter transporter
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC6A2 (Hs)
RESOLUTE SLC6A2 (Hs)
Other databases
Alphafold P23975 (Hs), O55192 (Mm)
ChEMBL Target CHEMBL222 (Hs), CHEMBL2370 (Mm)
DrugBank Target P23975 (Hs)
Ensembl Gene ENSG00000103546 (Hs), ENSMUSG00000055368 (Mm), ENSRNOG00000016311 (Rn)
Entrez Gene 6530 (Hs), 20538 (Mm), 83511 (Rn)
Human Protein Atlas ENSG00000103546 (Hs)
KEGG Gene hsa:6530 (Hs), mmu:20538 (Mm), rno:83511 (Rn)
OMIM 163970 (Hs)
Pharos P23975 (Hs)
UniProtKB P23975 (Hs), O55192 (Mm)
Wikipedia SLC6A2 (Hs)
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
(-)-adrenaline Substrate is endogenous in the given species Hs -
(-)-noradrenaline Substrate is endogenous in the given species Hs -
dopamine Substrate is endogenous in the given species Hs -
MPP+ Hs -
methamphetamine Hs -
amphetamine Hs -
Stoichiometry Click here for help
1 noradrenaline: 1 Na+:1 Cl- [8]

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]mazindol Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Inhibition 9.3 pKd 18
⤷ pKd 9.3 (Kd 5x10-10 M) [18]
protriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pKd 22
⤷ pKd 8.9 (Kd 1.41x10-9 M) [22]
atomoxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pKd 5
⤷ pKd 8.7 (Kd 2.03x10-9 M) [5]
[3H]nisoxetine Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Inhibition 8.4 pKd
⤷ pKd 8.4 (Kd 4x10-9 M)
clomipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKd 22
⤷ pKd 7.4 (Kd 3.8x10-8 M) [22]
nefazodone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.4 pKd 5
⤷ pKd 6.4 (Kd 3.6x10-7 M) [5]
Description: Dissociation constant of [3H]- nisoxatine vs. nefazodone.
mazindol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.9 pKi
⤷ pKi 8.9 (Ki 1.26x10-9 M)
desipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pKi 16
⤷ pKi 8.7 (Ki 2.1x10-9 M) [16]
nisoxetine Small molecule or natural product Hs Inhibition 8.4 pKi
⤷ pKi 8.4 (Ki 3.98x10-9 M)
lofepramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pKi 22
⤷ pKi 8.3 (Ki 5.4x10-9 M) [22]
duloxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKi 17
⤷ pKi 8.2 (Ki 5.97x10-9 M) [17]
nortriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKi 7
⤷ pKi 8.2 (Ki 6.3x10-9 M) [7]
protriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pKi 13
⤷ pKi 8.2 (Ki 6.8x10-9 M) [13]
H05 Small molecule or natural product Click here for species-specific activity table Rn Inhibition 8.2 pKi 28
⤷ pKi 8.2 (Ki 6.72x10-9 M) [28]
nomifensine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pKi
⤷ pKi 8.1 (Ki 7.94x10-9 M)
reboxetine Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.0 pKi 27
⤷ pKi 8.0 (Ki 1x10-8 M) [27]
maprotiline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.9 pKi 9
⤷ pKi 7.9 (Ki 1.2x10-8 M) [9]
N-desalkylquetiapine Small molecule or natural product Hs Inhibition 7.9 pKi 10
⤷ pKi 7.9 (Ki 1.2x10-8 M) [10]
amoxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.9 pKi 3
⤷ pKi 7.9 (Ki 1.3x10-8 M) [3]
imipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKi
⤷ pKi 7.8 (Ki 1.6x10-8 M)
mianserin Small molecule or natural product Approved drug Click here for species-specific activity table Rn Inhibition 7.6 pKi 14
⤷ pKi 7.6 (Ki 2.6x10-8 M) [14]
Description: Inhibition of [3H]NE uptake into rat synaptosomes
doxepin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pKi 3
⤷ pKi 7.5 (Ki 2.9x10-8 M) [3]
dosulepin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pKi 22
⤷ pKi 7.3 (Ki 4.6x10-8 M) [22]
ziprasidone Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inhibition 7.3 pKi 1
⤷ pKi 7.3 (Ki 4.8x10-8 M) [1]
dexamfetamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pKi 2
⤷ pKi 7.0 (Ki 1.01x10-7 M) [2]
dexmethylphenidate Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inhibition 6.6 pKi 11
⤷ pKi 6.6 (Ki 2.7x10-7 M) [11]
Description: Displacement of [3H]nisoxetine from NET in Sprague-Dawley rat cortical tissue.
amitriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pKi 2
⤷ pKi 6.5 (Ki 3.33x10-7 M) [2]
bupropion Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.4 pKi 12
⤷ pKi 6.4 (Ki 4.41x10-7 M) [12]
desvenlafaxine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition <6.2 pKi 6
⤷ pKi <6.2 (Ki >6.5x10-7 M) [6]
quetiapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.0 pKi 10
⤷ pKi 6.0 (Ki 9.27x10-7 M) [10]
trimipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.6 pKi 22
⤷ pKi 5.6 (Ki 2.45x10-6 M) [22]
solriamfetol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.4 pKi 4
⤷ pKi 5.4 (Ki 3.7x10-6 M) [4]
Description: In a radioligand binding assay using HEK293 cells expressing hNET.
sibutramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.3 pKi 3
⤷ pKi 5.3 (Ki 5.619x10-6 M) [3]
tapentadol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.1 pKi 24
⤷ pKi 5.1 (Ki 8.8x10-6 M) [24]
phenelzine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <5.0 pKi 22
⤷ pKi <5.0 (Ki >1x10-5 M) [22]
citalopram Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <3.0 pKi 29
⤷ pKi <3.0 (Ki >1x10-3 M) [29]
Description: Inhibition of [3H]dopamine uptake at human NET expressed in COS7 cells.
milnacipran Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 25
⤷ pIC50 9.1 (IC50 7.94x10-10 M) [25]
protriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.8 pIC50 15
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [15]
Description: Inhibition of [3H]nisoxetine binding to CHO cells expressing hNET.
norzotepine Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 20
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [20]
levomilnacipran Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 26
⤷ pIC50 7.4 (IC50 4x10-8 M) [26]
methylphenidate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pIC50
⤷ pIC50 7.2 (IC50 6.1x10-8 M)
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 20
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [20]
venlafaxine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pIC50 19
⤷ pIC50 6.3 (IC50 5.35x10-7 M) [19]
toludesvenlafaxine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.1 pIC50 21
⤷ pIC50 6.1 (IC50 7.63x10-7 M) [21]
solriamfetol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.4 pIC50 4
⤷ pIC50 5.4 (IC50 4.4x10-6 M) [4]
Description: In a NE reuptake assay in HEK293 cells expressing hNET.
View species-specific inhibitor tables
Inhibitor Comments
Protriptyline has also been shown to inhibit uptake of 5-HT in platelet rich human plasma [23].
Venlafaxine has a lower IC50 for SERT than for NET, therefore SERT has been tagged as the drug's primary target.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Orthostatic intolerance
OMIM: 604715

References

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