IndraLab

Statements

KCNH2 activates dTDP. 7 / 7
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"Sparfloxacin is a fluoroquinone antibiotic and HERG channel antagonist that is known to cause QT prolongation, Tdp and ventricular fibrillation [XREF_BIBR, XREF_BIBR]."
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"Despite being of such importance for drug discovery, the relevance and impact of hERG data are sometimes misinterpreted, as there are drugs that block the hERG coded ion channel but do not cause TdP, and drugs that cause TdP but do not block the hERG channel."
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"In the second step, the role of non hERG channels to modulate TdP risk are considered by constructing classifiers based on direct or derived features at critical hERG block concentrations that generates EADs in the computational cardiac cell models."
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"XREF_BIBR Loss-of-function mutations in hERG cause a reduction in the I Kr current of up to 97%, XREF_BIBR which causes QT prolongation, and usually increases risk of TdP."
29456831
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"Drugs that cause TdP block hERG cardiac potassium channels, but not all drugs that block hERG cause TdP XREF_BIBR."
33605379
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"In the case of adding calcium channel blocking activity, this might lead to lowered blood pressure or negative inotropy; thus, the mixture of hERG blocking activity with calcium channel blockade might have to be reserved for those patients who are already administered such drugs (e.g., verapamil), such as patients with concomitant hypertension.hERG blocking drugs could also be made safer by identification of those patients most susceptible to hERG induced TdP and then limiting the drugs to those patients who are predicted to tolerate the drug well."
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"To date, in patients with LQT2, the majority of mutations in hERG increase the transmural dispersion of repolarization and eventually induce prolongation of the QT interval, a notched T wave, re-entry and TdP."
26847485