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Compound Detail

CHEMBL1175

DULOXETINE
💊 Approved Drug
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💊 Approved Drug
CNCC[C@H](Oc1cccc2ccccc12)c1cccs1

Basic Information

ChEMBL ID CHEMBL1175
Name DULOXETINE
Phase Approved
Structure Type MOL
InChI Key ZEUITGRIYCTCEM-KRWDZBQOSA-N
Therapeutic ✓ Yes

Known Names

Duloxetina Duloxetine LY-248686 LY248686
20
Targets
101
Activities
3
Assay Types
6
PK Parameters
20
Publications
4
Known Names
20
Indications

Molecular Properties

297.4
MW (Da)
4.63
ALogP
3
HBA
1
HBD
21.3
PSA (Ų)
0.72
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2004
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -oxetine
USAN Year 1992

Extended Properties

Molecular Formula C18H19NOS
MW 297.42
Aromatic Rings 3
Heavy Atoms 21
NP-Likeness -0.54

Indications

Anxiety Anxiety Disorders Back Pain Biliary Dyskinesia Burning Mouth Syndrome Cognitive Dysfunction Dementia Depressive Disorder Depressive Disorder Depressive Disorder, Major Diabetic Neuropathies Diabetic Neuropathies Fibromyalgia Low Back Pain Osteoarthritis Osteoarthritis, Knee Parkinson Disease Peripheral Nervous System Diseases Schizophrenia Shoulder Pain

ATC Classification

N06AX21
duloxetine
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOANALEPTICS

Activity Summary

IC50 61 meas. best 9.5
Ki 39 meas. best 10.09
EC50 1 meas. best 4.74

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Sodium-dependent serotonin transporter
CHEMBL313
Ki 10.09 9.215 0.1 2
Sodium-dependent serotonin transporter
CHEMBL228
Ki 9.62 8.795 0.2 8
Sodium-dependent serotonin transporter
CHEMBL228
IC50 9.5 8.3908 0.3 13
Unchecked
CHEMBL612545
Ki 9.1 8.1875 0.8 4
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 8.8 7.8215 1.6 13
Transporter
CHEMBL6184
Ki 8.52 8.2433 3.0 3
Rattus norvegicus
CHEMBL376
Ki 8.34 7.5233 4.6 3
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 8.34 7.893 4.6 10
Sodium-dependent dopamine transporter
CHEMBL238
Ki 6.62 6.4633 240.0 9
Sodium-dependent dopamine transporter
CHEMBL338
IC50 6.43 6.43 370.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 6.36 6.36 440.0 2
Sodium-dependent dopamine transporter
CHEMBL238
IC50 6.23 6.0988 590.0 8
Cytochrome P450 2D6
CHEMBL289
IC50 6.0 5.825 1000.0 4
Voltage-gated L-type calcium channel
CHEMBL2095229
IC50 5.55 5.55 2800.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.39 5.39 4100.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.3 5.1667 5011.9 3
Cytochrome P450 1A2
CHEMBL3356
IC50 5.28 5.28 5300.0 2
Serine hydroxymethyltransferase, mitochondrial
CHEMBL4295747
IC50 5.16 5.16 6918.3 1
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 5.1 4.95 7943.3 2
Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK)
CHEMBL2221347
IC50 5.0 5.0 10000.0 1
Unchecked
CHEMBL612545
EC50 4.74 4.74 18330.0 1
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL1940
IC50 4.6 4.3 25118.9 2
Cytochrome P450 2C9
CHEMBL3397
IC50 4.54 4.54 29000.0 2
Unchecked
CHEMBL612545
IC50 4.32 4.205 48110.0 2
A-type voltage-gated potassium channel KCND3
CHEMBL1964
IC50 4.0 4.0 100000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 38.0 mL.min-1.g-1 Homo sapiens
CL 178.0 mL.min-1.kg-1 Rattus norvegicus
F 22.0 % Rattus norvegicus
t1/2 - - Homo sapiens
T1/2 2.0 hr Homo sapiens
T1/2 1.5 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Sodium-dependent serotonin transporter Ki = 0.082 nM 10.09 Displacement of [3H]-citalopram from Sprague-Dawley rat brain SERT after 1 hr 24900709
Sodium-dependent serotonin transporter Ki = 0.24 nM 9.62 Displacement of [3H]citalopram from human SERT transfected in HEK293 cells after... 24900709
Sodium-dependent serotonin transporter IC50 = 0.3162 nM 9.5 Inhibition of human recombinant SERT expressed in HEK293 cells assessed as inhib... 23347683
Sodium-dependent serotonin transporter Ki = 0.5012 nM 9.3 Inhibition of SERT 19592243
Sodium-dependent serotonin transporter Ki = 0.8 nM 9.1 Ability to inhibit the reuptake of 5-HT at human serotonin transporter 14643350
Unchecked Ki = 0.8 nM 9.1 Binding affinity for 5-hydroxytryptamine transporter 15454233
Sodium-dependent serotonin transporter Ki = 0.79 nM 9.1 Ability to inhibit [3H]paroxetine binding to cloned human serotonin (5-HT) trans... 15177457
Unchecked Ki = 1.24 nM 8.91 Displacement of [3H]-nisoxetine from Sprague-Dawley rat brain NET after 1 hr 24900709
Sodium-dependent noradrenaline transporter IC50 = 1.585 nM 8.8 Inhibition of human recombinant NET expressed in HEK293 cells assessed as inhibi... 23347683
Sodium-dependent serotonin transporter IC50 = 2.3 nM 8.64 Displacement of [3H]citalopram from human SERT transfected in HEK293 cells after... 24900709
Transporter Ki = 3.0 nM 8.52 Displacement of [3H]nisoxetine from rat NET in rat cerebral cortex 20945906
Sodium-dependent serotonin transporter IC50 = 3.0 nM 8.52 Inhibition of serotonin uptake at human SERT expressed in JAR cells 18771916
Sodium-dependent serotonin transporter IC50 = 3.0 nM 8.52 Inhibition of serotonin uptake at human SERT expressed in human JAR cells 19329313
Sodium-dependent serotonin transporter IC50 = 3.0 nM 8.52 Inhibition of human SERT expressed in human JAR cells 20378347
Transporter Ki = 3.9 nM 8.41 Inhibition of rat NET 23084899
Sodium-dependent noradrenaline transporter IC50 = 4.0 nM 8.4 Inhibition of norepinephrine uptake at human NET expressed in MDCK cells 18771916
Sodium-dependent noradrenaline transporter IC50 = 4.0 nM 8.4 Inhibition of norepinephrine uptake at human NET expressed in MDCK-Net6 cells 19329313
Sodium-dependent serotonin transporter IC50 = 4.0 nM 8.4 Inhibition of [3H]5-HT uptake at human 5HTT expressed in HEK293 cells 19359175
Sodium-dependent noradrenaline transporter IC50 = 4.0 nM 8.4 Inhibition of human NET transfected in MDCK-Net6 cells 20378347
Sodium-dependent serotonin transporter Ki = 4.6 nM 8.34 Displacement of [3H]citalopram from SERT in Sprague-dawley rat frontal cortex by... 19038547

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 60
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
24900709 10.1021/ml400049p Unchecked 4
20691589 10.1016/j.bmcl.2010.07.020 Rattus norvegicus 4
23347683 10.1016/j.bmcl.2012.12.061 Rattus norvegicus 4
25087753 10.1016/j.vascn.2014.07.002 Voltage-gated inwardly rectifying potassium channel KCNH2 3
15454233 10.1016/j.bmcl.2004.08.005 Unchecked 3
37468498 10.1038/s41467-023-40064-9 Cannabinoid receptor 1 3
14643350 10.1016/j.bmcl.2003.08.079 Rattus norvegicus 3
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 3
24900709 10.1021/ml400049p Sodium-dependent serotonin transporter 3
19592243 10.1016/j.bmcl.2009.06.076 Caco-2 3
20014752 10.1021/tx900326k Hepatotoxicity 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2A 3
23347683 10.1016/j.bmcl.2012.12.061 ADMET 2
24900709 10.1021/ml400049p Rattus norvegicus 2
23347683 10.1016/j.bmcl.2012.12.061 Liver microsomes 2
25087753 10.1016/j.vascn.2014.07.002 Voltage-dependent L-type calcium channel subunit alpha-1C 2
24900709 10.1021/ml400049p Sodium-dependent noradrenaline transporter 2
25087753 10.1016/j.vascn.2014.07.002 Sodium channel protein type 5 subunit alpha 2

Data from ChEMBL 36 via Core Engine