Results 81 to 90 of about 1,529,868 (197)

Implementation of the In Vitro Seizure Liability Assay (iLAseizure) in Drug Discovery and Development: Mechanism of Action Case Studies

Pharmacology Research &Perspectives, Volume 14, Issue 5, October 2026.
ABSTRACT Central nervous system (CNS) liabilities remain a significant cause of attrition during small molecule drug development. We previously developed the in vitro seizure liability assay (iLAseizure), a new approach methodology (NAM) comprising a human induced pluripotent stem cell neuron microelectrode array (MEA) assay coupled with a panel of ...
Kimberly Rockley, Ruth Roberts, Hannah Jennings, Karen Jones, Magali‐Anne Maizières, Michael Morton   +5 more
wiley   +1 more source

hERG S4-S5 linker acts as a voltage-dependent ligand that binds to the activation gate and locks it in a closed state

Scientific Reports, 2017
Delayed-rectifier potassium channels (hERG and KCNQ1) play a major role in cardiac repolarization. These channels are formed by a tetrameric pore (S5–S6) surrounded by four voltage sensor domains (S1-S4).
Olfat A. Malak, Zeineb Es-Salah-Lamoureux, Gildas Loussouarn   +2 more
doaj   +1 more source

Application of an Open‐Source Modular Framework for Pharmacokinetic, Pharmacodynamic, and Safety Simulations to Anti‐Tuberculosis Drugs

CPT: Pharmacometrics &Systems Pharmacology, Volume 15, Issue 10, October 2026.
ABSTRACT Tuberculosis (TB) treatment requires long‐term multidrug regimens where dosing, efficacy, and safety optimization remain challenging. This tutorial establishes an integrated, open‐source, modular framework connecting high‐throughput PBPK (HT‐PBPK) simulations, mechanistic PBPK models, pharmacodynamic endpoints, and safety predictions for anti ...
Marco Siccardi, Nina Nauwelaerts, Raphaëlle Lesage, Diane Lefaudeux, Vanessa Baier, Venetia Karamitsou, Cleo Demeester, Miao‐Chan Huang, Alexander Kulesza, Stephan Schaller   +9 more
wiley   +1 more source

Chlorine Position Governs the Multitarget Bioactivity of Phenylhydrazines: In Vitro Antioxidant, Anti‐Inflammatory, Anti‐Tyrosinase and Antibacterial Evaluation Supported by DFT and Molecular Docking

ChemistrySelect, Volume 11, Issue 37, 6 October 2026.
Positional chlorination emerges as a key determinant of multitarget activity in phenylhydrazines. The para‐chloro derivative H3 shows the strongest anti‐inflammatory response, notable antibacterial activity, favorable ADMET behavior, and high COX‐2 affinity. DFT descriptors and molecular docking rationalize these substitution‐dependent effects, linking
L. Aouachria, S. Issadi, H. Debab, I. Selatnia, A.G. Soliman, K. Metwally, O. M. A. Khamaysa, Han‐seung Lee, Hassane Lgaz   +8 more
wiley   +1 more source

Hydroxyzine, a First Generation H1-Receptor Antagonist, Inhibits Human Ether-a-go-go–Related Gene (HERG) Current and Causes Syncope in a Patient With the HERG Mutation

Journal of Pharmacological Sciences, 2008
QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well as intake of drugs known to affect a cardiac K+ channel encoded by human ether-a-go-go–related gene ...
Tomoko Sakaguchi, Hideki Itoh, Wei-Guang Ding, Keiko Tsuji, Iori Nagaoka, Yuko Oka, Takashi Ashihara, Makoto Ito, Yoshihiro Yumoto, Naoko Zenda, Yukei Higashi, Youichi Takeyama, Hiroshi Matsuura, Minoru Horie   +13 more
doaj   +1 more source

Rosemary metabolite carnosic acid opens Kv1.1 via its voltage sensor and corrects Kv1.1‐linked episodic ataxia in mice

British Journal of Pharmacology, Volume 183, Issue 20, Page 6179-6198, October 2026.
Background and Purpose Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder caused primarily by loss‐of‐function mutations in the voltage‐gated potassium channel Kv1.1 (KCNA1). Small molecules that restore Kv1.1 activity hold promise as targeted therapies for EA1, yet current pharmacological strategies remain limited ...
Rían W. Manville, Ryan F. Yoshimura, Hanh A. Nguyen, Ruiming Zhao, Derk J. Hogenkamp, Steve A. N. Goldstein, Geoffrey W. Abbott   +6 more
wiley   +1 more source

AttenhERG: a reliable and interpretable graph neural network framework for predicting hERG channel blockers

Journal of Cheminformatics
Cardiotoxicity, particularly drug-induced arrhythmias, poses a significant challenge in drug development, highlighting the importance of early-stage prediction of human ether-a-go-go-related gene (hERG) toxicity.
Tianbiao Yang, Xiaoyu Ding, Elizabeth McMichael, Frank W. Pun, Alex Aliper, Feng Ren, Alex Zhavoronkov, Xiao Ding   +7 more
doaj   +1 more source

Determining properties of human‐induced pluripotent stem cell‐derived cardiomyocytes using spatially resolved electromechanical metrics

The Journal of Physiology, Volume 604, Issue 19, Page 8069-8099, 1 October 2026.
Abstract figure legend In this study, we use human‐induced pluripotent stem cell‐derived cardiomyocyte (hiPSC‐CM) experiments and computational modelling to identify the mechanism of action of drug compounds. In the hiPSC‐CM experiments, optical measurements of cell collections are recorded in the baseline case and after drug exposure.
Karoline Horgmo Jæger, Verena Charwat, Kevin E. Healy, Samuel Wall, Aslak Tveito   +4 more
wiley   +1 more source

Plectasin, First Animal Toxin-Like Fungal Defensin Blocking Potassium Channels through Recognizing Channel Pore Region

Toxins, 2015
The potassium channels were recently found to be inhibited by animal toxin-like human β-defensin 2 (hBD2), the first defensin blocker of potassium channels. Whether there are other defensin blockers from different organisms remains an open question. Here,
Fang Xiang, Zili Xie, Jing Feng, Weishan Yang, Zhijian Cao, Wenxin Li, Zongyun Chen, Yingliang Wu   +7 more
doaj   +1 more source

Identification of Sodium/Myo‐Inositol Transporter 1 as a Major Determinant of Arterial Contractility

The FASEB Journal, Volume 40, Issue 18, 30 September 2026.
The tonicity‐responsive enhancer binding‐protein (TonEBP) and serum glucocorticoid kinase (SGK) sense a rise in extracellular hypertonicity resulting in an increase SMIT1 membrane abundance in vascular smooth muscle cells. SMIT1 associates with Kv7.4/5, Gβγ, and KCNE4, promoting hyperpolarization, reduced voltage‐gated calcium channel (VGCC) opening ...
Elizabeth A. Forrester, Skye Lau, Miguel Benitez‐Angeles, Christopher J. Garland, Vincenzo Barrese, Anthony P. Albert, Iain A. Greenwood   +6 more
wiley   +1 more source