Blocking of the Human Ether-à-go-go-Related Gene Channel by Imatinib Mesylate
TLDR
Two S6 domain mutants, F652A and Y656A, attenuated IM-induced inhibition of WT I(HERG), providing a molecular mechanism for the cardiac side effects during the clinical administration of IM.Citations
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Cardiovascular safety of tyrosine kinase inhibitors: with a special focus on cardiac repolarisation (QT interval)
TL;DR: There is now a persuasive case for a regulatory requirement to study TKIs systematically for these effects, since most of these novel drugs are studied in trials with relatively small sample sizes and approved on an expedited basis, there is also a compelling case for their effective pharmacovigilance.
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Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall Risk/Benefit
Rashmi R. Shah,Joel Morganroth +1 more
TL;DR: The cardiovascular safety of tyrosine kinase inhibitors is reviewed, including the post-marketing data concerning their pro-arrhythmic effects, and the risks of arterial thromboembolic events (ATEs) associated with these agents are summarised.
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Incidence and relevance of QTc-interval prolongation caused by tyrosine kinase inhibitors
Jacqueline S. L. Kloth,Anna Pagani,Michiel C. Verboom,Alberto Malovini,Carlo Napolitano,Wim H. J. Kruit,Stefan Sleijfer,Neeltje Steeghs,Alberto Zambelli,Ron H.J. Mathijssen +9 more
TL;DR: These observations show that most TKIs significantly increase the QTc interval, and particularly in vemurafenib-treated patients, the incidence of patients at risk for arrhythmias is increased.
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Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives.
Jialin Duan,Jingwen Tao,Maocai Zhai,Chengpeng Li,Ning Zhou,Jiagao Lv,Lin Wang,Li Lin,Rong Bai +8 more
TL;DR: The mechanism of QT interval prolongation, risk factors for TdP and the QT toxicity of anticancer drugs as well as its management are reviewed.
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Lovastatin blocks Kv1.3 channel in human T cells: a new mechanism to explain its immunomodulatory properties
Ning Zhao,Qian Dong,Cheng Qian,Sen Li,Qiongfeng Wu,Dan Ding,Jing Li,Bin-bin Wang,Kefang Guo,Jiang-jiao Xie,Xiang Cheng,Yuhua Liao,Yimei Du +12 more
TL;DR: It is found that Lovastatin can exert immunodulatory properties through the new mechanism of blocking Kv1.3 channel in human T cells, and its new immunomodulatory mechanism is clarified.
References
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Journal ArticleDOI
A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel
TL;DR: The finding that HERG encodes IKr channels provides a mechanistic link between certain forms of inherited and acquired LQT, and that an additional subunit may be required for drug sensitivity.
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hERG potassium channels and cardiac arrhythmia
TL;DR: Insights gained from the crystal structures of other potassium channels have helped understanding of the block of hERG channels and the mechanisms of gating.
Journal Article
Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT)
TL;DR: The data indicate that compared with doxazosin, chlorthalidone reduces the risk of combined CVD events, particularly CHD death/nonfatal MI, in high-risk hypertensive patients.
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Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet
Michele Baccarani,Jorge E. Cortes,Fabrizio Pane,Dietger Niederwieser,Giuseppe Saglio,Jane F. Apperley,Francisco Cervantes,Michael W. Deininger,Alois Gratwohl,François Guilhot,Andreas Hochhaus,Mary M. Horowitz,Timothy P. Hughes,Hagop M. Kantarjian,Richard A. Larson,Jerald P. Radich,Bengt Simonsson,Richard T. Silver,John M. Goldman,Rüdiger Hehlmann +19 more
TL;DR: Imatinib should be continued indefinitely in optimal responders and second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
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Cardiotoxicity of the cancer therapeutic agent imatinib mesylate
Risto Kerkelä,Luanda Grazette,Rinat Yacobi,Cezar Iliescu,Richard D. Patten,Cara Beahm,Brian Walters,Sergei P. Shevtsov,Sergei P. Shevtsov,Stephanie Pesant,Fred J. Clubb,Anthony Rosenzweig,Robert N. Salomon,Richard A. Van Etten,Joseph Alroy,Jean-Bernard Durand,Thomas Force,Thomas Force +17 more
TL;DR: Cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib, where cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death.