hERG Binding Assays for the Identification of Potentially Cardiotoxic Compounds
نویسندگان
چکیده
A [I]-BeKm-1 saturation binding assay was performed on hERG K channel membranes using FlashBlue beads. An average Bmax value of 0.6 pmol/mg (considering a counting efficiency of 40% for FlashBlue beads) was obtained, with a Kd value of 0.17 nM. Panel A shows a saturation binding curve. The corresponding Scatchard analysis is illustrated in panel B. The data presented is derived from single site fitting.
منابع مشابه
PredictorTM hERG Fluorescence Polarization Assay Kit performed on the PHERAstar/PHERAstar Plus
The potential for cardiotoxic side-effects continues to challenge the development of small molecule based therapies. These intolerable side-effects are often precipitated by drug-induced long QT syndrome (LQT), which is often linked to blocking the human ether-a-go-go related gene (hERG) potassium channel. Although patch-clamp electrophysiology remains the gold standard for determining the inte...
متن کاملHighlight report: Cardiotoxicity screening
have published a review about identification of cardiotoxic compounds by rapid screening methods (Li et al., 2015). Cardiotoxicity is one of the most frequent causes for withdrawal of drugs from the market and also during drug development (MacDonald and Robertson, 2009; Apostolakis et al., 2013; Li et al., 2015). Totally, 81 drugs have been taken from the market between 1990 and 2013 (Li et al....
متن کاملIdentification of Mycobacterium tuberculosis adherence-mediating components: a review of key methods to confirm adhesin function
Anti-adhesion therapy represents a potentially promising avenue for the treatment and prevention of tuberculosis in a post-antibiotic era. Adhesins are surface-exposed microbial structures or molecules that enable pathogenic organisms to adhere to host surfaces, a fundamental step towards host infection. Although several Mycobacterium tuberculosis adhesins have been identified, it is predicted ...
متن کاملStereoselective block of hERG channel by bupivacaine scrutinized at molecular level.
In the heart, the hERG voltage-gated potassium channel mediates the I(Kr) current, which is crucial for the duration of cardiac action potential. Undesired block of the channel may prolong the QT interval with increased risk of malignant ventricular arrhythmia called torsades de pointes. Although the molecular determinants of hERG block are intensively studied, stereoselectivity has been poorly...
متن کاملEvaluation of the rubidium efflux assay for preclinical identification of HERG blockade.
Inhibition of the delayed-rectifier potassium channel current, human ether-a-go-go (hERG), by pharmaceutical agents can lead to acquired long QT syndrome and the generation of potentially lethal arrhythmias and sudden death. There remains an unmet need for higher-throughput assays to screen compounds in preclinical development for the potential to block hERG and cause QT prolongation. We evalua...
متن کامل