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Compound Detail

CHEMBL726

FLUPHENAZINE
💊 Approved Drug
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💊 Approved Drug
OCCN1CCN(CCCN2c3ccccc3Sc3ccc(C(F)(F)F)cc32)CC1

Basic Information

ChEMBL ID CHEMBL726
Name FLUPHENAZINE
Phase Approved
Structure Type MOL
InChI Key PLDUPXSUYLZYBN-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Flufenazina Fluphenazine NSC-62323
63
Targets
135
Activities
3
Assay Types
7
PK Parameters
20
Publications
3
Known Names
2
Indications

Molecular Properties

437.5
MW (Da)
4.31
ALogP
5
HBA
1
HBD
29.9
PSA (Ų)
0.73
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1959
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral

Flags

Black Box Warning

Extended Properties

Molecular Formula C22H26F3N3OS
MW 437.53
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -1.28

Indications

Psychotic Disorders Schizophrenia

ATC Classification

N05AB02
fluphenazine
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOLEPTICS

Activity Summary

IC50 72 meas. best 9.23
Ki 61 meas. best 9.7
EC50 2 meas. best 5.4

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
D(3) dopamine receptor
CHEMBL234
Ki 9.7 8.8933 0.2 3
D(2) dopamine receptor
CHEMBL217
Ki 9.27 8.9833 0.5 3
D(3) dopamine receptor
CHEMBL234
IC50 9.23 9.23 0.6 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 8.84 8.18 1.5 2
D(2) dopamine receptor
CHEMBL217
IC50 8.79 8.79 1.6 1
Histamine H1 receptor
CHEMBL231
Ki 8.33 7.8033 4.7 3
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 8.29 8.29 5.1 1
Alpha-1A adrenergic receptor
CHEMBL229
Ki 8.19 8.19 6.5 1
5-hydroxytryptamine receptor 7
CHEMBL3155
Ki 8.1 8.1 8.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 8.07 8.07 8.6 1
Alpha-1A adrenergic receptor
CHEMBL319
Ki 8.02 8.02 9.6 1
D(1A) dopamine receptor
CHEMBL2056
Ki 7.96 7.1533 11.0 3
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 7.89 7.49 13.0 2
Alpha-1D adrenergic receptor
CHEMBL223
Ki 7.8 7.8 16.0 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 7.72 7.72 19.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
IC50 7.7 7.7 20.0 1
D(1B) dopamine receptor
CHEMBL1850
Ki 7.68 7.68 21.0 2
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 7.66 7.6 22.0 2
D(1A) dopamine receptor
CHEMBL2056
IC50 7.64 7.64 23.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 7.62 7.52 24.0 2
Alpha-1A adrenergic receptor
CHEMBL319
IC50 7.62 7.62 24.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 7.6 7.6 25.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
IC50 7.54 7.54 29.0 1
Alpha-1D adrenergic receptor
CHEMBL223
IC50 7.48 7.48 33.0 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 7.47 7.47 34.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.46 7.46 35.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 7.41 7.41 39.0 1
Histamine H1 receptor
CHEMBL231
IC50 7.4 7.4 40.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
IC50 7.28 7.28 52.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 7.17 7.17 67.0 1
Adenylate cyclase
CHEMBL2095179
IC50 7.1 7.1 80.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 7.1 6.8 80.0 2
Unchecked
CHEMBL612545
Ki 7.01 5.6033 97.0 6
D(4) dopamine receptor
CHEMBL219
Ki 6.89 6.29 130.0 2
5-hydroxytryptamine receptor 1A
CHEMBL214
Ki 6.84 6.84 145.7 1
Alpha-2C adrenergic receptor
CHEMBL1916
IC50 6.81 6.81 154.0 1
Unchecked
CHEMBL612545
IC50 6.8 5.4244 158.0 9
Alpha-2A adrenergic receptor
CHEMBL1867
IC50 6.67 6.67 215.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 6.32 6.32 484.0 1
Plasmodium falciparum
CHEMBL364
IC50 6.3 6.3 500.0 2
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 6.19 6.19 646.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 6.1 6.1 793.0 1
Androgen receptor
CHEMBL3072
Ki 6.1 6.1 800.0 1
5-hydroxytryptamine receptor 1B
CHEMBL3459
Ki 6.06 6.06 869.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 6.03 6.03 939.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 6.0 6.0 1002.0 1
Histamine H2 receptor
CHEMBL1941
Ki 5.92 5.92 1205.0 1
Histamine H2 receptor
CHEMBL1941
IC50 5.91 5.91 1226.0 1
Sodium-dependent serotonin transporter
CHEMBL228
IC50 5.83 5.83 1492.0 1
Sodium-dependent dopamine transporter
CHEMBL238
Ki 5.79 5.79 1631.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 1581.0 mL.min-1.kg-1 Homo sapiens
CL 121.0 uL.min-1.(10^6cells)-1 Homo sapiens
CL 71.6 uL.min-1.(10^6cells)-1 Homo sapiens
CL 9.9 mL.min-1.kg-1 Homo sapiens
F 2.7 % Homo sapiens
Fu 0.012 - Not specified
Fu 0.455 - Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
D(3) dopamine receptor Ki = 0.202 nM 9.7 DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone) -
D(2) dopamine receptor Ki = 0.539 nM 9.27 DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone) -
D(3) dopamine receptor IC50 = 0.594 nM 9.23 DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone) -
D(2) dopamine receptor Ki = 1.44 nM 8.84 Binding affinity to D2 receptor (unknown origin) assessed as inhibition constant 39038276
5-hydroxytryptamine receptor 2A Ki = 1.458 nM 8.84 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
D(2) dopamine receptor Ki = 1.44 nM 8.84 Displacement of [3H]spiperone from human dopamine D2 receptor expressed in CHO c... 19091563
D(2) dopamine receptor IC50 = 1.616 nM 8.79 DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone) -
D(3) dopamine receptor Ki = 3.2 nM 8.49 Binding affinity to D3 receptor (unknown origin) assessed as inhibition constant 39038276
D(3) dopamine receptor Ki = 3.21 nM 8.49 Displacement of [3H]spiperone from human dopamine D3 receptor expressed in CHO c... 19091563
Histamine H1 receptor Ki = 4.662 nM 8.33 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
5-hydroxytryptamine receptor 2A IC50 = 5.104 nM 8.29 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Alpha-1A adrenergic receptor Ki = 6.5 nM 8.19 Binding affinity to alpha1A adrenergic receptor (unknown origin) assessed as inh... 39038276
5-hydroxytryptamine receptor 7 Ki = 8.0 nM 8.1 Binding affinity to 5HT7 receptor (unknown origin) assessed as inhibition consta... 39038276
Sigma non-opioid intracellular receptor 1 Ki = 8.575 nM 8.07 DRUGMATRIX: Sigma1 radioligand binding (ligand: [3H] Haloperidol) -
Alpha-1A adrenergic receptor Ki = 9.578 nM 8.02 DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin) -
D(1A) dopamine receptor Ki = 11.0 nM 7.96 DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390) -
Alpha-2B adrenergic receptor Ki = 13.0 nM 7.89 DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscin... -
Alpha-1D adrenergic receptor Ki = 16.0 nM 7.8 DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin) -
Alpha-1B adrenergic receptor Ki = 19.0 nM 7.72 DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin) -
Sigma non-opioid intracellular receptor 1 IC50 = 20.0 nM 7.7 DRUGMATRIX: Sigma1 radioligand binding (ligand: [3H] Haloperidol) -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1381
- 10.6019/CHEMBL3885881 Rattus norvegicus 463
- 10.5281/zenodo.13943903 ADMET 86
31158845 10.1038/s41586-019-1291-3 ADMET 79
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
19223631 10.1128/aac.00926-08 Candida albicans 10
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
- 10.6019/CHEMBL4808148 Histone deacetylase 6 4
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
853510 10.1021/jm00215a024 Unchecked 3
11716514 10.1006/bbrc.2001.6000 ATP-dependent translocase ABCB1 3
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2A 3
18363346 10.1021/jm7012453 Rattus norvegicus 3
21998403 10.1124/dmd.111.042309 ADMET 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 Cannabinoid receptor 1 3
9457238 10.1021/jm960814j Mus musculus 3

Data from ChEMBL 36 via Core Engine