Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 23 for “"hERG"”.
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Febrile Temperature Facilitates Degradation of Human Ether-a-Go-Go-Related Gene (hERG) Channels
The human ether-a-go-go-related gene (hERG) encodes the α subunit of the rapidly activating delayed rectifier K+ channel (IKr), which plays an essential role in human cardiac repolarization. Dysfunction of hERG caused by genetic mutations or drug-mediated effects can lead to long QT syndrome …
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Investigating the novel interaction between hERG and the Fc region of IgG and its consequences
The human ether-a-go-go related gene (hERG; KCNH2) encodes the pore-forming subunit of the Kv11.1 channel which conducts the rapidly activating delayed rectifier potassium current (IKr). Impairment of hERG function is responsible for the form of acquired long QT syndrome (LQTS) observed in certain …
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Determinantes moleculares de la modulación de la apertura y cierre del canal de K+ hERG por dominios citoplásmicos
El canal humano hERG pertenece a la familia eag (KCNH) de canales de potasio dependientes de voltaje. Debido a su peculiar comportamiento como "rectificador anómalo", hERG juega un papel crucial en la finalización del potencial de acción ventricular cardíaco, pero también un papel fundamental en la …
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Trafficking motifs in potassium channels
… by insulin hyper-secretion and hypoglycemia. The hERG (human ether-a-go-go related gene) potassium channels,encoded by the KCNH2 gene, contribute to the rapidly activating delayed rectifier K+ current (IKr), which is responsible for rapid repolarisation of the cardiac action potential. Decreased …
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Palladium(II)-Catalysed sp 3 C–H Functionalisation of Hindered Amines and its Application in Synthesis of Astemizole Analogues
… agent which suffers from undesired hERG activity. The increased steric bulk around the tertiary amine, coupled with introduction of a polar hydroxyl group via the C–H acetoxylation reaction, is proposed to reduce binding to the hERG channel. The hERG profile of this analogue is not …
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Structure activity and structure property relationships of antimalarial imidazopyridazines
… and off-target human ether-a-go-go-related gene (hERG) potassium ion channel liabilities. Towards improving solubility and de-risking the hERG liability, a series of analogues was designed and synthesised. Structure-Activity Relationship (SAR) and Structure-Property Relationship (SPR) studies …
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Computational approaches to predicting drug induced toxicity
… mutagenicity, carcinogenicity, inhibition of the hERG ion channel and the associated arrhythmia - Torsades de Pointes. A consensus model was developed based on Derek for WindowsTM and Toxtree and used to filter compounds as part of a collaborative effort resulting in the identification of …
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Physicochemical, biological and β-haematin inhibiting activity of pyrido-dibemequines, pyrido[1,2-α]benzimidazoles and their derivatives
… Predicted human-Ether-a-Go-Go-Related Gene (hERG) channel inhibition pIC₅₀ ranged between 6.2 and 6.6, and correlated strongly with the cLogP and molecular weight. The derivatives were also highly susceptibility to microsomal metabolism, with N-dealkylation identified as the main …
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Design, synthesis, and structure-activity relationship studies of dual Plasmodium falciparum phosphatidylinositol 4-kinase and cGMP-dependent protein kinase inhibitors
… SI > 100), low human ether-a-go-go-related gene (hERG) activity (IC50 > 10 µM) and high metabolic stability against human, rat, and mouse (H/R/M) liver microsomes (> 75% remaining after 30-min incubation). Selected compounds from the series also showed the potential for transmission blockade with …
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Antimalarial imidazopyridazines and aminopyrazines: synthesis, physicochemical optimization and structure-activity relationships
… risk as shown from its inhibition of the hERG (human ether-a-go-go-related gene)-encoded potassium channel. Further medicinal chemistry optimization led to identification of other derivatives which, albeit exhibiting complete cure of P. berghei-infected mice, still displayed poor …
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Development of in silico models for the prediction of toxicity incorporating ADME information
… exemplified by human Ether-à-go-go-Related Gene (hERG) channel inhibition, was also explored. A number of novel structural alerts for hERG toxicity were developed based on groups of structurally similar compounds. Finally, the importance of predicting potential ecotoxicological effects of drugs …
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Bridging molecular and systems scales in membrane biology
… of conformational change in channels, such as hERG (Chapter 5), and the ability of growth factors to bind and activate growth factor receptors, such as VEGFR-2 (Chapter 6). The last chapter showcases the application of different computational methods, which integrates molecular simulation and …
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Investigating calcium channel blockers as antimalarials
… and the effect compound 4c has on the hERG channel was carried out to develop a preliminary understanding of the mode of action of the compound. Finally, optimisation experiments to develop a flow cytometry-based assay that would detect fluctuations in calcium levels within infected red …
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Rutas de transducción de señales y procesos de fosforilización implicados en la regulación de canales erg por TRH
… hemos encontrado 14 sitios de fosforilación de hERG, dos de los cuales (S250 y S261) no habían sido identificados previamente. El estado de fosforilación de otros dos de esos sitios (S239 y S1137) aumenta notablemente tras el tratamiento con TRH. A partir de estos sitios de fosforilación …
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Repositioning of astemizole for malaria
… inhibit the human ether-á-go-go-related gene (hERG) encoded potassium (K+) channels. This liability led to the withdrawal of AST in most countries during the late 1970's and it is still being discontinued for use in some countries to date.
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Antimalarial benzimidazoles and related structures incorporating an intramolecular hydrogen bonding motif: medicinal chemistry and mechanistic studies
… drug astemizole, were tested against the hERG (human ether-a-go-go-related)-encoded potassium ion channel. These analogues expressed >40% inhibition against the hERG ion channel at the highest test concentration with potencies between 0.96 and 13.24 µM. Regardless, these compounds showed …
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Characterization of the Central Cavity of a Potassium Channel: Helix Dipoles, Conformational Plasticity and Inhibition
… cavity block may be conserved, including BK and HERG channels. Thus, this new conformation of block could have important implications for the pharmacology of human potassium channels. This work furthers our understanding of electrostatic interactions, structural plasticity, and a new mode of …
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Semi-synthesis, synthesis and preclinical evaluation of sigma receptors ligands for the treatment of neuropathic pain [Semi-sintesi, sintesi e valutazione preclinica dei ligandi dei recettori sigma per il trattamento del dolore neuropatico]
… anche una ridotta inibizione del canale hERG K+ (IC50 = 5.8 μM). Inoltre, ligandi che presentano il diazaspiro[4.4]nonano come nucleo ed i gruppi fenilacetato e fenilacetammidico, quali AD263 (Ki S1R = 79.9 nM; Ki S2R = 4.1 nM), AD223 (Ki S1R = 62.7 nM; Ki S2R = 4.1 nM) e AD359 (Ki S1R = …
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An investigation into nucleic acid binding compounds
… these compounds that can lower affinity to the hERG ion channel, a major pharmaceutical anti-target. Whilst a range of our compounds display significant activity against Gram positive bacteria, very few have significant activity against Gram negative species. In order to investigate this, a …
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Computational analyses on the structure-function relation in ion channels
… (involved in tumour-cell proliferation) and hErg (important in the cardiac cycle) for several pharmaceutical drugs was compared. Both experimental measurements and molecular modeling were used in order to identify differences in the blocking mechanism of the two channels, which could be …
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