astemizole   Click here for help

GtoPdb Ligand ID: 2603

Synonyms: Hismanal®
Approved drug PDB Ligand
astemizole is an approved drug
Compound class: Synthetic organic
Comment: 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 Astemizole use as an antihistamine was withdrawn from the US market in 1999 as it caused arrhythmias, probably due to blocking the hERG potassium channel (Kv11.1) [5].

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) [3]. 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) [1], and that this action destabilizes PRC2 and reduces its methylation activity.
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Ligand Activity Visualisation Charts

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View interactive charts of activity data across species

astemizole is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 42.32
Molecular weight 458.25
XLogP 5.81
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COc1ccc(cc1)CCN1CCC(CC1)Nc1nc2c(n1Cc1ccc(cc1)F)cccc2
Isomeric SMILES COc1ccc(cc1)CCN1CCC(CC1)Nc1nc2c(n1Cc1ccc(cc1)F)cccc2
InChI InChI=1S/C28H31FN4O/c1-34-25-12-8-21(9-13-25)14-17-32-18-15-24(16-19-32)30-28-31-26-4-2-3-5-27(26)33(28)20-22-6-10-23(29)11-7-22/h2-13,24H,14-20H2,1H3,(H,30,31)
InChI Key GXDALQBWZGODGZ-UHFFFAOYSA-N
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes
Withdrawn drug? Yes
IUPAC Name Click here for help
1-[(4-fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl]benzimidazol-2-amine
International Nonproprietary Names Click here for help
INN number INN
4755 astemizole
Synonyms Click here for help
Hismanal®
Database Links Click here for help
Specialist databases
GPCRdb Ligand astemizole
Other databases
BindingDB Ligand 24226
CAS Registry No. 68844-77-9
ChEBI CHEBI:2896
ChEMBL Ligand CHEMBL296419
DrugBank Ligand DB00637
DrugCentral Ligand 249
GtoPdb PubChem SID 135649968
PubChem CID 2247
RCSB PDB Ligand XB7
Search Google for chemical match using the InChIKey GXDALQBWZGODGZ-UHFFFAOYSA-N
Search Google for chemicals with the same backbone GXDALQBWZGODGZ
Search PubMed clinical trials astemizole
Search PubMed titles astemizole
Search PubMed titles/abstracts astemizole
UniChem Compound Search for chemical match using the InChIKey GXDALQBWZGODGZ-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey GXDALQBWZGODGZ-UHFFFAOYSA-N
Wikipedia Astemizole

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Tocris
Astemizole (links to external site)
Cat. No. 3489