Journal ArticleDOI
Removal of hERG potassium channel affinity through introduction of an oxygen atom: Molecular insights from structure-activity relationships of strychnine and its analogs.
Chunhua Yuan,Zheng-Yi Luo,Ying Zhou,Sheng Lei,Changxi Xu,Chao Peng,Shu-Ji Li,Xiao-Wen Li,Xin-Hong Zhu,Tian-Ming Gao +9 more
TLDR
This study suggests that introduction of an oxygen to compensate for the N+ − charge could be a useful strategy for reducing hERG potency and increasing the safety margin of alkaloid‐type compounds in drug development.About:
This article is published in Toxicology and Applied Pharmacology.The article was published on 2018-12-01. It has received 7 citations till now. The article focuses on the topics: Brucine & hERG.read more
Citations
More filters
Journal ArticleDOI
Human ether-à-go-go-related potassium channel: exploring SAR to improve drug design.
Maria Maddalena Cavalluzzi,Paola Imbrici,Roberta Gualdani,Angela Stefanachi,Giuseppe Felice Mangiatordi,Giovanni Lentini,Orazio Nicolotti +6 more
TL;DR: This study surveys the most recent advances regarding hERG by focusing on SAR in the attempt to elucidate, at a molecular level, off-target and on-target actions of potential hERG binders, which are highly promiscuous and largely varying in structure.
Journal ArticleDOI
Risk Compounds, Preclinical Toxicity Evaluation, and Potential Mechanisms of Chinese Materia Medica-Induced Cardiotoxicity.
Jie Zhou,Fu Peng,Xiao-Yu Cao,Xiaofang Xie,Dayi Chen,Lian Yang,Chaolong Rao,Cheng Peng,Xiaoqi Pan +8 more
TL;DR: In this article, a review aimed to summarize the risk compounds, preclinical toxicity evaluation, and potential mechanisms of CMM-induced cardiotoxicity, and relevant articles published on the PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases for the latest twenty years were searched and manually extracted.
Journal ArticleDOI
Effects and mechanism of gating modifier spider toxins on the hERG channel.
TL;DR: Structural-function analysis of the gating modifier toxins suggested that the functional bioactive surface binding to the hERG channel consists of a conserved hydrophobic patch, surrounding acidic residues (Glu10 in JZTX-XIII, Glu11 in JzTX-I), and basic residues which may be different from residuesbinding to the Kv2.1 channel.
Journal ArticleDOI
A Combination of In Silico ADMET Prediction, In Vivo Toxicity Evaluation, and Potential Mechanism Exploration of Brucine and Brucine N-oxide—A Comparative Study
TL;DR: In this paper , a comparative study of BRU and BNO was performed by combination analysis of in-silico ADMET prediction, in vivo toxicity evaluation, and potential action mechanism exploration.
Journal ArticleDOI
Chemical constituents, pharmacological action, antitumor application, and toxicity of Strychnine Semen from Strychnons pierriana A.W.Hill.: A review.
TL;DR: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases, providing a review for further research and development of Strychnos resources as discussed by the authors .
References
More filters
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.
Journal ArticleDOI
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome
Mark E. Curran,Igor Splawski,Katherine W. Timothy,Vincent Gm,Eric D. Green,Keating Mt,Keating Mt +6 more
TL;DR: In this article, the authors investigated patients with long QT syndrome (LQT), an inherited disorder causing sudden death from a ventricular tachyarrythmia, torsade de pointes.
Journal ArticleDOI
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 ArticleDOI
HERG, a Human Inward Rectifier in the Voltage-Gated Potassium Channel Family
TL;DR: The properties of HERG channels are consistent with the gating properties of Eag-related and other outwardly rectifying, S4-containing potassium channels, but with the addition of an inactivation mechanism that attenuates potassium efflux during depolarization.
Journal ArticleDOI
A structural basis for drug-induced long QT syndrome
TL;DR: Alanine-scanning mutagenesis is used to determine the structural basis for high-affinity drug block of HERG channels by MK-499, a methanesulfonanilide antiarrhythmic drug, and suggest a possible structural explanation for how so many commonly used medications block HERG but not other Kv channels.