Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL296419

ASTEMIZOLE
💊 Approved Drug
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
💊 Approved Drug
COc1ccc(CCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1

Basic Information

ChEMBL ID CHEMBL296419
Name ASTEMIZOLE
Phase Approved
Structure Type MOL
InChI Key GXDALQBWZGODGZ-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Astemizol Astemizole GNF-Pf-2461 Hismanal NSC-329963 NSC-759570 Pollon-eze R 43,512
76
Targets
204
Activities
4
Assay Types
16
PK Parameters
20
Publications
8
Known Names
1
Indications
1
Mechanisms

Molecular Properties

458.6
MW (Da)
5.35
ALogP
5
HBA
1
HBD
42.3
PSA (Ų)
0.39
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1988
Availability Withdrawn
Chirality Achiral

Routes of Administration

Oral

Flags

Withdrawn
USAN Year 1979

Extended Properties

Molecular Formula C28H31FN4O
MW 458.58
Aromatic Rings 4
Heavy Atoms 34
NP-Likeness -1.37

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Histamine H1 receptor antagonist ANTAGONIST Histamine H1 receptor

Indications

Hypersensitivity

ATC Classification

R06AX11
astemizole
Level 1: RESPIRATORY SYSTEM
Level 2: ANTIHISTAMINES FOR SYSTEMIC USE

Drug Warnings

Withdrawn
General Warning
Increased risk of QT prolongation with concomitant administration of oral or parenteral formulations of azole antifungals, macrolide antibiotics except azithromycin, selective serotonin reuptake inhib...
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Fatal arrhythmia; Drug Interaction
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Cardiotoxic effects
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
General Warning
Fatal arrhythmia; Drug Interaction
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Rare but serious side-effects on heart, primary changes in heart rhythm
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Associated with adverse drug reactions including irregular heart rhythms and severe allergic reactions if taken at higher than recommended doses or in conjunction with some other drugs including antih...
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Serious adverse cardiovascular reactions
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
General Warning
Several adverse reactions
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
cardiotoxicity
Prolongation of the QT-interval and ventricular arrhythmias; Increased risk of QT prolongation with concomitant administration of oral or parenteral formulations of azole antifungals, macrolide antibi...
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998
Withdrawn
immune system toxicity
Associated with adverse drug reactions including irregular heart rhythms and severe allergic reactions if taken at higher than recommended doses or in conjunction with some other drugs including antih...
Country: Malaysia; Singapore; Armenia; United Arab Emirates; Brunei; Mauritius; Bhutan; Tanzania; Spain; Chile; Argentina; Philippines; United States; South Africa; Brazil   Year: 1998

Activity Summary

IC50 124 meas. best 9.05
Ki 62 meas. best 8.79
EC50 14 meas. best 8.72
Kd 4 meas. best 8.42

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 9.05 7.9479 0.9 24
Histamine H1 receptor
CHEMBL231
Ki 8.79 8.6633 1.6 3
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
EC50 8.72 8.72 1.9 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
Ki 8.68 8.154 2.1 5
Histamine H1 receptor
CHEMBL3943
Kd 8.42 8.42 3.8 1
ADMET
CHEMBL612558
Kd 8.3 8.3 5.0 1
No relevant target
CHEMBL2362975
Kd 8.26 8.26 5.5 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 8.25 8.25 5.6 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 8.13 8.13 7.5 1
Alpha-1A adrenergic receptor
CHEMBL319
Ki 8.0 8.0 9.9 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 7.92 7.92 12.0 1
Histamine H1 receptor
CHEMBL231
IC50 7.85 7.85 14.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 7.7 7.7 20.0 1
Alpha-1A adrenergic receptor
CHEMBL319
IC50 7.62 7.62 24.0 1
Unchecked
CHEMBL612545
Ki 7.52 6.0944 30.0 9
Unchecked
CHEMBL612545
IC50 7.48 5.4575 33.0 12
RBL-2H3
CHEMBL614632
IC50 7.27 7.0567 53.3 3
Plasmodium falciparum
CHEMBL364
IC50 7.07 6.656 86.0 10
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.03 7.03 94.0 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 7.02 7.02 95.0 1
Sigma intracellular receptor 2
CHEMBL4105907
Ki 7.02 7.02 95.0 2
Plasmodium berghei
CHEMBL612653
IC50 6.94 6.7033 114.0 3
D(3) dopamine receptor
CHEMBL234
Ki 6.83 6.83 148.0 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 6.76 6.76 172.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 6.75 6.75 179.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 6.75 6.75 178.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 6.59 6.59 259.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 6.59 6.59 257.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 6.54 6.54 285.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 6.52 6.1 300.0 3
Alpha-1D adrenergic receptor
CHEMBL223
Ki 6.42 6.42 378.0 1
D(3) dopamine receptor
CHEMBL234
IC50 6.36 6.36 436.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 6.36 6.36 438.0 1
Plasmodium falciparum
CHEMBL364
EC50 6.35 6.25 447.0 2
Muscarinic acetylcholine receptor M5
CHEMBL2035
Ki 6.3 6.3 505.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 6.3 6.3 501.0 1
Mu-type opioid receptor
CHEMBL233
Ki 6.22 6.22 606.0 1
5-hydroxytryptamine receptor 1B
CHEMBL3459
Ki 6.2 6.2 630.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 6.16 6.16 700.0 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
IC50 6.15 6.15 703.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
IC50 6.12 6.12 767.0 1
Alpha-1D adrenergic receptor
CHEMBL223
IC50 6.11 6.11 769.0 1
Sodium-dependent dopamine transporter
CHEMBL238
Ki 6.1 6.1 793.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
IC50 6.08 6.08 840.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 6.03 5.9433 944.0 3
Substance-K receptor
CHEMBL2327
Ki 6.0 6.0 995.0 1
Sodium-dependent dopamine transporter
CHEMBL238
IC50 6.0 6.0 998.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 5.97 5.97 1066.0 1
Voltage-gated L-type calcium channel
CHEMBL2095229
IC50 5.96 5.96 1100.0 1
SARS-CoV-2
CHEMBL4303835
EC50 5.96 5.96 1100.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 11.01 ng.hr.mL-1 Homo sapiens
CL 136.0 mL.min-1.g-1 Homo sapiens
CL 66.0 mL.min-1.g-1 Homo sapiens
CL 3.05 uL/min Homo sapiens
Fu 0.011 - Rattus norvegicus
Fu 0.004 - Rattus norvegicus
T1/2 26.0 hr Homo sapiens
T1/2 0.025 hr Homo sapiens
T1/2 0.06667 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Rattus norvegicus
Vd 48.0 L.kg-1 -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 0.9 nM 9.05 Inhibition of hERG potassium channel in HEK293 cells by patch clamp assay 16722631
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 0.9 nM 9.05 Inhibitory activity against Potassium channel HERG 12747773
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 0.9 nM 9.05 K+ channel blocking activity in human embryonic kidney cells expressing HERG Kv1... 12190308
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 0.912 nM 9.04 Inhibition of human ERG in MCF7 cells 19110341
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 0.912 nM 9.04 Inhibition of human voltage-gated potassium channel subunit Kv11.1 (ERG K+ chann... 15745831
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1.5 nM 8.82 Inhibitory concentration against IKr potassium channel 15324906
Histamine H1 receptor Ki = 1.611 nM 8.79 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Voltage-gated inwardly rectifying potassium channel KCNH2 EC50 = 1.9 nM 8.72 Binding affinity to human ERG by fluorescence polarization assay 24900814
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 2.1 nM 8.68 Displacement of [3H]Astemizole from human recombinant ERG expressed in HEK293 ce... 23403082
Histamine H1 receptor Ki = 2.089 nM 8.68 Displacement of [3H]mepyramine from human H1R expressed in Sf9 cells co-expressi... 21944853
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 2.6 nM 8.59 Displacement of [3H]Astemizole from human recombinant ERG expressed in HEK293 ce... 23403082
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 2.9 nM 8.54 Binding affinity at hERG expressed in HEK293 cells by fluorescence polarization ... 17536794
Histamine H1 receptor Ki = 3.0 nM 8.52 Binding affinity towards histamine H1 receptor 12747773
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 3.31 nM 8.48 Inhibition of human ERG assessed as reduction in channel current by automated pa... 27017549
Histamine H1 receptor Kd = 3.802 nM 8.42 Antagonist activity at H1R in guinea pig ileum assessed as inhibition of histami... 21944853
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 4.0 nM 8.4 Inhibition of human ERG expressed in CHO K1 cells measured after 4 min by QPatch... 38628794
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 4.2 nM 8.38 Inhibition of human ERG expressed in CHO-K1 cells by Q-patch clamp assay 36507890
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 4.2 nM 8.38 Inhibition of human ERG stably expressed in CHO-K1 cells at -90 mV holding poten... 34413963
ADMET Kd = 5.012 nM 8.3 pA2 value is determined compared to standard H1-antagonists 7562938
No relevant target Kd = 5.5 nM 8.26 Dissociation constant (KD) of the compound 7562938

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4295262 Unchecked 36
16472241 10.2174/1570163043334794 Hepatotoxicity 18
25369470 10.1021/jm501230c Polycomb protein EED 16
25369470 10.1021/jm501230c NON-PROTEIN TARGET 12
12699389 10.1021/jm021012t ATP-dependent translocase ABCB1 10
3934386 10.1021/jm00150a029 Rattus norvegicus 8
25369470 10.1021/jm501230c DB 7
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 6
29042223 10.1016/j.bmc.2017.10.004 Plasmodium falciparum 5
3934386 10.1021/jm00150a029 Cavia porcellus 5
21841964 10.1021/ml200117z Liver microsomes 5
3934387 10.1021/jm00150a030 Cavia porcellus 4
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 4
33619967 10.1021/acs.jmedchem.0c02011 ADMET 4
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 4
10052971 10.1021/jm981079+ Mus musculus 4
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4

Data from ChEMBL 36 via Core Engine