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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

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)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
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 21
pKd 8.9 (Kd 1.41x10-9 M) [21]
atomoxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table 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 21
pKd 7.4 (Kd 3.8x10-8 M) [21]
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 21
pKi 8.3 (Ki 5.4x10-9 M) [21]
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 27
pKi 8.2 (Ki 6.72x10-9 M) [27]
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 Hs Inhibition 8.0 pKi 26
pKi 8.0 (Ki 1x10-8 M) [26]
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 21
pKi 7.3 (Ki 4.6x10-8 M) [21]
ziprasidone Small molecule or natural product Approved drug 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 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 21
pKi 5.6 (Ki 2.45x10-6 M) [21]
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 23
pKi 5.1 (Ki 8.8x10-6 M) [23]
phenelzine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <5.0 pKi 21
pKi <5.0 (Ki >1x10-5 M) [21]
citalopram Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <3.0 pKi 28
pKi <3.0 (Ki >1x10-3 M) [28]
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 24
pIC50 9.1 (IC50 7.94x10-10 M) [24]
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 25
pIC50 7.4 (IC50 4x10-8 M) [25]
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]
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 [22].
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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