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Compound Detail

CHEMBL623

NEFAZODONE
💊 Approved Drug
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💊 Approved Drug
CCc1nn(CCCN2CCN(c3cccc(Cl)c3)CC2)c(=O)n1CCOc1ccccc1

Basic Information

ChEMBL ID CHEMBL623
Name NEFAZODONE
Phase Approved
Structure Type MOL
InChI Key VRBKIVRKKCLPHA-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Nefazodona Nefazodone
20
Targets
27
Activities
4
Assay Types
16
PK Parameters
20
Publications
2
Known Names
3
Indications

Molecular Properties

470.0
MW (Da)
3.55
ALogP
7
HBA
0
HBD
55.5
PSA (Ų)
0.45
QED
0
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1994
Availability Withdrawn
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Withdrawn Natural Product
USAN Year 1984

Extended Properties

Molecular Formula C25H32ClN5O2
MW 470.02
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -1.96

Indications

Depressive Disorder Cocaine-Related Disorders Marijuana Abuse

ATC Classification

N06AX06
nefazodone
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOANALEPTICS

Drug Warnings

Withdrawn
hepatotoxicity
acute hepatic failure
Country: Canada; Spain; Turkey   Year: 2003
Withdrawn
hepatotoxicity
life-threatening hepatotoxicity
Country: Canada; Spain; Turkey   Year: 2003
Withdrawn
hepatotoxicity
acute hepatic failure
Country: Canada; Spain; Turkey   Year: 2003

Activity Summary

IC50 12 meas. best 7.82
Ki 8 meas. best 8.24
Kd 4 meas. best 6.8
EC50 3 meas. best 5.1

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 8.24 8.24 5.8 1
5-hydroxytryptamine receptor 2A
CHEMBL322
Ki 8.15 8.15 7.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 7.82 6.82 15.0 2
Liver
CHEMBL613642
IC50 7.5 7.5 32.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 7.28 7.28 52.0 1
Sodium-dependent serotonin transporter
CHEMBL313
Ki 6.86 6.86 137.0 1
5-hydroxytryptamine receptor 1A
CHEMBL214
Kd 6.8 6.8 158.5 1
Sodium-dependent serotonin transporter
CHEMBL228
Kd 6.7 6.7 200.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 6.54 6.54 290.0 1
Sodium-dependent dopamine transporter
CHEMBL238
Kd 6.44 6.44 360.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Kd 6.44 6.44 360.0 1
Norepinephrine transporter
CHEMBL304
Ki 6.24 6.24 570.0 1
Cytochrome P450 3A4
CHEMBL340
Ki 6.0 6.0 1000.0 1
Acetylcholinesterase
CHEMBL220
IC50 5.98 5.98 1037.0 1
Sodium-dependent dopamine transporter
CHEMBL338
Ki 5.62 5.62 2380.0 1
Bile salt export pump
CHEMBL6020
IC50 5.38 5.224 4200.0 5
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 5.33 5.33 4700.0 1
Trypanosoma cruzi
CHEMBL368
EC50 5.1 5.1 8000.0 1
ADMET
CHEMBL612558
EC50 4.82 4.82 15000.0 1
Bile salt export pump
CHEMBL2073674
IC50 4.76 4.76 17400.0 1
Unchecked
CHEMBL612545
EC50 4.37 4.37 42350.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.15 4.15 71000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 6815.29 ng.hr.mL-1 Homo sapiens
CL 7.5 mL.min-1.kg-1 Homo sapiens
CL 7.1 mL.min-1.kg-1 Homo sapiens
CL 7.5 mL.min-1.kg-1 Homo sapiens
CL 7.5 mL.min-1.kg-1 Homo sapiens
CL 7.5 mL.min-1.kg-1 Homo sapiens
Cmax 6800.0 nM Homo sapiens
F 20.0 % Homo sapiens
Fu 0.009 - -
Fu 0.008 - -
Fu 0.009 - Homo sapiens
Fu 0.01 - Homo sapiens
Fu 0.01 - Homo sapiens
MRT 1.1 hr Homo sapiens
T1/2 1.2 hr Homo sapiens
T1/2 1.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
5-hydroxytryptamine receptor 2A Ki = 5.8 nM 8.24 Binding affinity to 5-HT2A 21823597
5-hydroxytryptamine receptor 2A Ki = 7.0 nM 8.15 Binding affinity to rat 5HT2A receptor 31537425
Cytochrome P450 3A4 IC50 = 15.0 nM 7.82 Time dependent inhibition of CYP3A4 in human liver microsomes 22409598
Liver IC50 = 31.97 nM 7.5 Induction of mitochondrial dysfunction in Sprague-Dawley rat liver mitochondria ... 24799086
5-hydroxytryptamine receptor 1A Ki = 52.0 nM 7.28 Binding affinity to rat 5HT1A receptor 31537425
Sodium-dependent serotonin transporter Ki = 137.0 nM 6.86 Inhibition of [3H]5-HT reuptake into rat frontal cortex synaptosomes 9871604
5-hydroxytryptamine receptor 1A Kd = 158.49 nM 6.8 Binding affinity to 5HT1A receptor 19754201
Sodium-dependent serotonin transporter Kd = 200.0 nM 6.7 Equilibrium dissociation constant (KD) for Competitive binding between [3H]- imi... 9871604
Sodium-dependent serotonin transporter Ki = 290.0 nM 6.54 Binding affinity to SERT 21823597
Sodium-dependent noradrenaline transporter Kd = 360.0 nM 6.44 Equilibrium dissociation constant (KD) for Competitive binding between [3H]- nis... 9871604
Sodium-dependent dopamine transporter Kd = 360.0 nM 6.44 Equilibrium dissociation constant (KD) for Competitive binding between [3H]WIN-3... 9871604
Norepinephrine transporter Ki = 570.0 nM 6.24 Inhibition of [3H]- NE reuptake into rat hippocampal synaptosomes 9871604
Cytochrome P450 3A4 Ki = 1000.0 nM 6.0 Time dependent inhibition of CYP3A4 22409598
Acetylcholinesterase IC50 = 1037.0 nM 5.98 Inhibition of AChE (unknown origin) 29429576
Cytochrome P450 3A4 IC50 = 1500.0 nM 5.82 Competitive inhibition of CYP3A4 in human liver microsomes 22409598
Sodium-dependent dopamine transporter Ki = 2380.0 nM 5.62 Inhibition of [3H]- DA reuptake into rat striatal synaptosomes 9871604
Bile salt export pump IC50 = 4200.0 nM 5.38 Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells ass... 21965623
ATP-dependent translocase ABCB1 IC50 = 4700.0 nM 5.33 TP_TRANSPORTER: inhibition of Rhodamine 123 transepithelial transport (basal to ... 11452702
Bile salt export pump IC50 = 6100.0 nM 5.21 Inhibition of human BSEP expressed in fall armyworm sf9 cell plasma membrane ves... 20829430
Bile salt export pump IC50 = 6110.0 nM 5.21 Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as... 23956101

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 89
31158845 10.1038/s41586-019-1291-3 ADMET 69
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
20070106 10.1021/jm901371v Homo sapiens 8
12061889 10.1021/jm0200409 ADMET 5
22409598 10.1021/jm300065h Cytochrome P450 3A4 4
18426954 10.1124/dmd.108.020479 ADMET 4
20014752 10.1021/tx900326k Hepatotoxicity 3
22409598 10.1021/jm300065h Homo sapiens 3
11452702 10.1177/00912700122010609 ATP-dependent translocase ABCB1 3
37468498 10.1038/s41467-023-40064-9 Cannabinoid receptor 1 3
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 3
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2A 3
24799086 10.1002/hep.27206 Homo sapiens 2
21965623 10.1124/dmd.111.040758 Bile salt export pump 2

Data from ChEMBL 36 via Core Engine