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 Astemizole use as an antihistamine was withdrawn from the US market in 1999 as it caused arrhythmias, probably due to blocking the hERG potassium channel (Kv11.1) [5].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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2D Structure
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Physico-chemical Properties
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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
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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)
Classification Click here for help
Compound class Synthetic organic
Approved drug? Yes
Withdrawn drug? Yes
IUPAC Name Click here for help
International Nonproprietary Names Click here for help
INN number INN
4755 astemizole
Synonyms Click here for help
Database Links Click here for help
Specialist databases
GPCRdb Ligand astemizole
Other databases
BindingDB Ligand 24226
CAS Registry No. 68844-77-9
ChEMBL Ligand CHEMBL296419
DrugBank Ligand DB00637
DrugCentral Ligand 249
GtoPdb PubChem SID 135649968
PubChem CID 2247
Search Google for chemical match using the InChIKey GXDALQBWZGODGZ-UHFFFAOYSA-N
Search Google for chemicals with the same backbone GXDALQBWZGODGZ
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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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Astemizole (links to external site)
Cat. No. 3489