General
Preferred name
ASTEMIZOLE
Synonyms
Histaminos ()
Paralergin ()
Laridal ()
R 43512 ()
Pollon-Eze ()
Hismanal ()
NSC-759570 ()
NSC-329963 ()
R 43,512 ()
GNF-Pf-2461 ()
P&D ID
PD009877
CAS
68844-77-9
Tags
natural product
drug
available
Approved by
FDA
First approval
1988
Drug Status
approved
withdrawn
Drug indication
Anti-Allergic
Allergic rhinitis
Antihistaminic
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Astemizole was originally identified as a histamine H1 receptor antagonist. Astemizole use as an antihistamine was withdrawn from the US market in 1999 as it caused arrhythmias, probably due to blocking the hERG potassium channel (Kv11.1) .
A 2014 publication showed that astemizole's anti-proliferative effects in cancer cells is due to disruption of a protein-protein interaction required for the formation of the active polycomb repressive complex 2 (PRC2) . PRC2 contains the histone methyltransferase EZH2, which is responsible for catalytic trimethylation of lysine 27 on histone H3 (H3K27me3), an epigenetic modification that is a hallmark of silent chromatin. Aberrant PRC2 activity is associated with cancer initiation and progression. Astemizole was shown to inhibit the interaction between EZH2 and a PRC2 structural protein called embryonic ectoderm development (EED) , and that this action destabilizes PRC2 and reduces its methylation activity. (GtoPdb)
A 2014 publication showed that astemizole's anti-proliferative effects in cancer cells is due to disruption of a protein-protein interaction required for the formation of the active polycomb repressive complex 2 (PRC2) . PRC2 contains the histone methyltransferase EZH2, which is responsible for catalytic trimethylation of lysine 27 on histone H3 (H3K27me3), an epigenetic modification that is a hallmark of silent chromatin. Aberrant PRC2 activity is associated with cancer initiation and progression. Astemizole was shown to inhibit the interaction between EZH2 and a PRC2 structural protein called embryonic ectoderm development (EED) , and that this action destabilizes PRC2 and reduces its methylation activity. (GtoPdb)
DESCRIPTION
Astemizole was withdrawn from the US market in 1999 as it caused arrhythmias, probably due to interaction with the hERG channel.
DESCRIPTION
Orally active, potent H1 antagonist. Also KV11.1 (hERG) channel blocker.
(Tocriscreen Plus)
DESCRIPTION
Potent, selective CCR1 antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Orally active, potent H1 antagonist. Also hERG K+ channel blocker.
(Tocriscreen Total)
DESCRIPTION
Astemizole is a potent and orally active nonsedating-type histamine H1 receptor antagonist with IC50 value of 4 nM. It competitively binds to histamine H1 receptor sites in the uterus, gastrointestinal tract, bronchial muscle and blood vessels. It suppresses the formation of edema and pruritus caused by histamine. It has antipruritic and anticholinergic effects. It is also a potent blocker of ether-a-go-go-related gene (ERG) potassium channel blocker with IC50 value of 0.9 nM. It exhibits antimalarial activity in multidrug resistant strains in vitro with IC50 value of 227-734 nM. It has the potential for combination therapy with antivancer drugs in resistant leukemia. It is considerably less potent at muscarinic acetylcholine receptors with Ki value of 2.4 µM. It may be used as a potential antineoplastic agent for decreasing proliferation of various cancer cells. It may be used as a pharmacological chaperone to restore protein function for some mutated forms of hERG channels and correct folding defects. It was developed by Johnson & Johnson.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
9
Organisms
5
Compound Sets
30
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMatrix
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
Withdrawn 2.0
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
32
Molecular Weight
458.25
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
8
Ring Count
5
Aromatic Ring Count
4
cLogP
5.35
TPSA
42.32
Fraction CSP3
0.32
Chiral centers
0.0
Largest ring
6.0
QED
0.39
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
GPCR/G protein
Membrane Transporter/Ion Channel
Immunology/Inflammation
Neuroscience
Neuronal Signaling
Target
H1 receptor
Potassium Channel
HRH1, KCNH1, KCNH2
Histamine Receptor
Histamine Receptor,Potassium Channel
Primary Target
Histamine H1 Receptors
MOA
Antagonist
Histamine Receptor antagonist
ATC
R06AX11
Toxicity type
cardiovascular
Therapeutic Class
Antiallergic Agents
Source data
