Displacement of [3H]pyrilamine from human recombinant histamine H1 receptor expressed in CHO cell by Betaplate scintillation counting
- Deposit:2010-07-08
- Modify:2022-08-30
Title: Structural determinants for histamine H(1) affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs.
Abstract: In the late 1980's reports linking the non-sedating antihistamines terfenadine and astemizole with torsades de pointes, a form of ventricular tachyarrhythmia that can degenerate into ventricular fibrillation and sudden death, appeared in the clinical literature. A substantial body of evidence demonstrates that the arrhythmogenic effect of these cardiotoxic antihistamines, as well as a number of structurally related compounds, results from prolongation of the QT interval due to suppression of specific delayed rectifier ventricular K+ currents via blockade of the hERG-IKr channel. In order to better understand the structural requirements for hERG and H(1) binding for terfenadine, a series of analogs of terfenadine has been prepared and studied in both in vitro and in vivo hERG and H(1) assays.
Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Journal: Bioorg Med Chem Lett
Year: 2009
Volume: 19
Issue: 17
First Page: 5043
Last Page: 5047
DOI: 10.1016/j.bmcl.2009.07.047
Target ChEMBL ID: CHEMBL231
ChEMBL Target Name: Histamine H1 receptor
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned
- PubChem
- ChEMBLLICENSEAccess to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).http://www.ebi.ac.uk/Information/termsofuse.html