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Compound Detail

CHEMBL479

THIORIDAZINE
💊 Approved Drug
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💊 Approved Drug
CSc1ccc2c(c1)N(CCC1CCCCN1C)c1ccccc1S2

Basic Information

ChEMBL ID CHEMBL479
Name THIORIDAZINE
Phase Approved
Structure Type MOL
InChI Key KLBQZWRITKRQQV-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Dl-thioridazine Mellaril-s Mellerette Melleril Novoridazine Rideril Sonapax Thioridazine Thioridazine prolongatum Thioril Tioridazina TP-21
67
Targets
146
Activities
3
Assay Types
11
PK Parameters
20
Publications
12
Known Names
6
Indications
3
Mechanisms

Molecular Properties

370.6
MW (Da)
5.89
ALogP
4
HBA
0
HBD
6.5
PSA (Ų)
0.62
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1962
Availability Withdrawn
Chirality Racemic

Routes of Administration

Oral

Flags

Black Box Warning Withdrawn Natural Product
USAN Year 1962

Extended Properties

Molecular Formula C21H26N2S2
MW 370.59
Aromatic Rings 2
Heavy Atoms 25
NP-Likeness -1.03

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serotonin 2a (5-HT2a) receptor antagonist ANTAGONIST 5-hydroxytryptamine receptor 2A
Serotonin 2c (5-HT2c) receptor antagonist ANTAGONIST 5-hydroxytryptamine receptor 2C
D2-like dopamine receptor antagonist ANTAGONIST D2-like dopamine receptor

Indications

Psychotic Disorders Anxiety Dementia Depressive Disorder Schizophrenia Leukemia, Myeloid, Acute

ATC Classification

N05AC02
thioridazine
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOLEPTICS

Drug Warnings

Withdrawn
cardiotoxicity
Cardiac arrythmias
Country: Worldwide   Year: 2005
Black Box Warning
General Warning
Country: United States

Activity Summary

IC50 104 meas. best 8.7
Ki 40 meas. best 8.9
Kd 2 meas. best 6.43

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 8.9 7.99 1.2 2
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 8.77 8.77 1.7 1
Muscarinic acetylcholine receptor
CHEMBL1907609
IC50 8.7 7.835 2.0 2
Alpha-1A adrenergic receptor
CHEMBL319
Ki 8.69 8.69 2.1 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 8.59 8.59 2.6 1
D(2) dopamine receptor
CHEMBL339
IC50 8.55 7.8475 2.8 4
Alpha-1D adrenergic receptor
CHEMBL223
Ki 8.54 8.54 2.9 1
D(3) dopamine receptor
CHEMBL234
Ki 8.47 8.47 3.4 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 8.36 8.36 4.4 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 8.33 8.33 4.7 1
Alpha-1A adrenergic receptor
CHEMBL319
IC50 8.29 8.29 5.1 1
Alpha-1D adrenergic receptor
CHEMBL223
IC50 8.23 8.23 5.9 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
Ki 8.18 8.18 6.6 1
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 8.15 8.15 7.0 1
L5178Y
CHEMBL614720
IC50 8.13 6.515 7.4 4
D(2) dopamine receptor
CHEMBL217
Ki 8.1 7.8633 8.0 3
Histamine H1 receptor
CHEMBL231
Ki 8.07 8.07 8.4 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
IC50 8.03 8.03 9.2 1
D(3) dopamine receptor
CHEMBL234
IC50 8.01 8.01 9.9 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 7.96 7.96 11.0 1
Adrenergic receptor alpha-1
CHEMBL1907610
IC50 7.77 7.3833 17.0 3
D(1A) dopamine receptor
CHEMBL265
IC50 7.76 6.9167 17.3 3
Serotonin 2 (5-HT2) receptor
CHEMBL2093870
IC50 7.75 7.485 18.0 2
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 7.72 7.72 19.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.64 7.64 23.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 7.6 7.6 25.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 7.48 6.9942 33.0 12
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 7.48 7.315 33.0 2
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 7.47 7.47 34.0 1
D(2) dopamine receptor
CHEMBL217
IC50 7.46 7.46 35.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 7.42 7.42 38.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 7.36 7.36 44.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 7.3 7.3 50.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
IC50 7.22 7.22 60.0 1
5-hydroxytryptamine receptor 7
CHEMBL3155
Ki 7.16 6.95 70.0 2
5-hydroxytryptamine receptor 6
CHEMBL3371
IC50 7.15 7.15 71.0 1
Histamine H1 receptor
CHEMBL231
IC50 7.14 7.14 72.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
IC50 7.1 7.1 80.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 7.09 7.09 82.0 1
Dopamine receptor
CHEMBL2093868
IC50 7.07 7.07 85.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
IC50 7.05 7.05 90.0 1
D(1A) dopamine receptor
CHEMBL2056
Ki 7.01 7.01 97.0 1
Histamine H1 receptor
CHEMBL4701
IC50 7.0 7.0 99.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
IC50 6.97 6.97 106.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 6.89 6.89 129.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
IC50 6.88 6.88 133.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 6.82 6.82 153.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
IC50 6.77 6.77 171.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 6.76 6.76 174.0 1
D(1A) dopamine receptor
CHEMBL2056
IC50 6.71 6.71 194.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 50.0 mL.min-1.g-1 Homo sapiens
CL 114.0 uL.min-1.(10^6cells)-1 Rattus norvegicus
F 49.0 % Homo sapiens
Fu 0.001 - Rattus norvegicus
Fu 0.002 - Rattus norvegicus
Fu 0.049 - Homo sapiens
Fu 0.00067 - Rattus norvegicus
Fu 0.001 - Rattus norvegicus
Fu 0.0003 - Sus scrofa
Fu 0.0031 - Rattus norvegicus
Vd 3333.0 L.kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
5-hydroxytryptamine receptor 2A Ki = 1.247 nM 8.9 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M1 Ki = 1.69 nM 8.77 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor IC50 = 2.0 nM 8.7 Displacement of [3H]quinuclidinyl benzilate (QNB) from Muscarinic acetylcholine ... 2892936
Alpha-1A adrenergic receptor Ki = 2.062 nM 8.69 DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin) -
Alpha-1B adrenergic receptor Ki = 2.597 nM 8.59 DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin) -
D(2) dopamine receptor IC50 = 2.8 nM 8.55 In vitro binding affinity against Dopamine receptor D2 by displacement of [3H]ha... 2888897
Alpha-1D adrenergic receptor Ki = 2.895 nM 8.54 DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin) -
D(3) dopamine receptor Ki = 3.36 nM 8.47 DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone) -
D(2) dopamine receptor IC50 = 4.0 nM 8.4 Displacement of [3H]haloperidol from Dopamine receptor D2 in rat brain 2892936
5-hydroxytryptamine receptor 2A IC50 = 4.366 nM 8.36 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Alpha-1B adrenergic receptor IC50 = 4.692 nM 8.33 DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin) -
Alpha-1A adrenergic receptor IC50 = 5.093 nM 8.29 DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin) -
Alpha-1D adrenergic receptor IC50 = 5.891 nM 8.23 DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin) -
Muscarinic acetylcholine receptor M5 Ki = 6.643 nM 8.18 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M1 IC50 = 7.019 nM 8.15 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
L5178Y IC50 = 7.43 nM 8.13 Cytotoxicity against multidrug resistance mouse L5178Y cells expressing human MD... 32871268
D(2) dopamine receptor Ki = 8.0 nM 8.1 Displacement of [3H]-Raclopride from human D2 receptor (unknown origin) expresse... 32526553
Histamine H1 receptor Ki = 8.412 nM 8.07 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Muscarinic acetylcholine receptor M5 IC50 = 9.246 nM 8.03 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
D(3) dopamine receptor IC50 = 9.892 nM 8.01 DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone) -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1392
- 10.6019/CHEMBL3885881 Rattus norvegicus 290
28964936 10.1016/j.ejmech.2017.09.014 Unchecked 184
26562541 10.1016/j.ejmech.2015.10.054 Mycobacterium tuberculosis 45
26197353 10.1021/acs.jmedchem.5b00428 Mycobacterium tuberculosis 43
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
18694955 10.1128/aac.00661-08 NON-PROTEIN TARGET 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
28964936 10.1016/j.ejmech.2017.09.014 Mycobacterium avium 8
1361578 10.1021/jm00102a002 Rattus norvegicus 7
32526553 10.1016/j.ejmech.2020.112420 Mycobacterium tuberculosis 7
31478 10.1021/jm00209a012 Rattus norvegicus 6
2869146 10.1021/jm00153a010 Rattus norvegicus 6
28039773 10.1016/j.ejmech.2016.12.042 Mycobacterium tuberculosis 5
2892936 10.1021/jm00397a032 Rattus norvegicus 4
2888897 10.1021/jm00393a021 Rattus norvegicus 4
19764786 10.1021/jm901036q Plasma 4
- 10.6019/CHEMBL3301361 ADMET 4

Data from ChEMBL 36 via Core Engine