Are hERG channel blockers also phospholipidosis inducers?
نویسندگان
چکیده
منابع مشابه
A k-nearest neighbor classification of hERG K+ channel blockers
A series of 172 molecular structures that block the hERG K(+) channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k-nearest neighbor model development. A consensus model constructed using Extended-CDK, PubChem and Substructure count fingerprint-based models was found to be a robust predictor of hERG activity. This consensus model...
متن کاملPredictive in silico modeling for hERG channel blockers.
hERG-mediated sudden death as a side effect of non-antiarrhythmic drugs has been receiving increased regulatory attention. Perhaps owing to the unique shape of the ligand-binding site and its hydrophobic character, the hERG channel has been shown to interact with pharmaceuticals of widely varying structure. Several in silico approaches have attempted to predict hERG channel blockade. Some of th...
متن کاملComputer simulations of structure-activity relationships for HERG channel blockers.
The hERG potassium channel is of major pharmaceutical importance, and its blockade by various compounds, potentially causing serious cardiac side effects, is a major problem in drug development. Despite the large amounts of existing biochemical data on blockade of hERG by drugs and druglike compounds, relatively little is known regarding the structural basis of binding of blockers to the channe...
متن کاملHERG and KvLQT1/IsK, the cardiac K+ channels involved in long QT syndromes, are targets for calcium channel blockers.
We examined the effects of the calcium channel blockers nitrendipine, diltiazem, verapamil, bepridil, and mibefradil on the cloned HERG and KvLQT1/IsK K+ channels. These channels generate the rapid and slow components of the cardiac delayed rectifier K+ current, and mutations can affect them, which leads to long QT syndromes. When expressed in transfected COS cells, HERG is blocked in a concent...
متن کاملA novel hypothesis for the binding mode of HERG channel blockers.
We present a new docking model for HERG channel blockade. Our new model suggests three key interactions such that (1) a protonated nitrogen of the channel blocker forms a hydrogen bond with the carbonyl oxygen of HERG residue T623; (2) an aromatic moiety of the channel blocker makes a pi-pi interaction with the aromatic ring of HERG residue Y652; and (3) a hydrophobic group of the channel block...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2013
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2013.06.034