IndraLab
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Ion channel inhibits KCNH2. 37 / 37
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sparser
"It exhibits a low human ether-a-go-go-related gene (hERG) ion channel inhibition, excellent systemic exposure, crosses the blood-brain barrier in mice when administered orally, and BKI-1553 treatment lead to reduced parasite burden in the brain, lungs and liver of T. gondii infected mice ( xref )."
sparser
"Accordingly, new chemical entities are typically screened for hERG ion channel inhibition early in the drug development process.[ xref ]The ability of TetM0 to inhibit the hERG ion channel (six concentrations from 0.008 μM to 25 μM) was evaluated via the patch-clamp technique (QPatch HTX)."
sparser
"The link between in vitro hERG ion channel inhibition and subsequent in vivo QT interval prolongation, a critical risk factor for the development of arrythmias such as Torsade de Pointes, is so well established that in vitro hERG activity alone is often sufficient to end the development of an otherwise promising drug candidate."
sparser
"The results indicate that considering only the hERG ion channel inhibition of only the parent drug is potentially misleading, and the inclusion of active metabolite data and the influence of other ion channel currents should be considered to improve the prediction of potential cardiac toxicity."
sparser
"TKI-induced arrhythmia is predominantly associated with direct ion channel inhibition of KCNH2 (Kv11.1) or the human ether-à-go-go (hERG) channel (see xref ). xref The hERG channel regulates K + efflux out of the cardiomyocyte during repolarization and comprises the “rapid” delayed rectifier K + current ( I Kr ) in intact heart myofibers."
sparser
"Acyclic CB[ n ]-type receptors are composed of a central glycoluril oligomer building block, two aromatic walls, and peripheral solubilizing groups which has allowed extensive structure-binding affinity relationships to be built up. xref – xref Our earliest acyclic CB[ n ]-type receptor ( ACB1 ) was based on glycoluril tetramer, o -xylylene walls, and peripheral carboxylic acids groups; ACB1 possessed poor aqueous solubility (≤ 2 mM). xref In contrast, host M1 with SO 3 Na groups displays an anomalously high solubility of 346 mM in water which enabled its use as a solubilizing excipient for insoluble drugs and was used to deliver albendazole to mice in vivo . xref , xref Host M1 was shown to be biocompatible according to the standard in vitro (e.g. metabolic and cell death, Ames test, lack of hERG ion channel inhibition) and in vivo (e.g. maximum tolerated dose, blood gas and blood pH, mean artertial pressue) assays. xref , xref More recently, we have shown that M1 and analogues function as in vivo reversal agents for neuromuscular block induced by rocuronium, vecuronium, and cisatracurium and for the hyperlocomotion induced by the drug of abuse methamphetamine. xref , xref , xref In ongoing work, we aim to optimize the structure of acyclic CB[ n ]-type receptors for use in these biomedical applications."
sparser
"As expected, the hERG ion channel is inhibited by E-4031 at nanomolar concentrations whereas no concentration dependent inhibition is observed for M3 at concentrations up to 25 μM. The calculated IC50 value for E-4031 is 267 nM whereas for M3 the IC50 is higher than 25 μM. Compounds with hERG ion channel inhibition IC50 values below 100 nM are classified as highly potent whereas those with IC50 values above 10 μM are categorized as having little to no inhibitory activity.[ xref ]Given the lack of hERG ion channel inhibition activity of M3 we proceeded to test the mutagenicity of M3 ."
sparser
"Numerous variants have been created, by us and others, that differ in the nature of the central glycoluril oligomer, the terminal aromatic walls, and the appended solubilizing groups. xref , xref Of the acyclic CB[n] based on glycoluril tetramer prepared to date, Tet1 and Tet2 have been used extensively because of their high binding affinity which has enabled their function as solubilizing excipients for insoluble drugs and as in vivo sequestration agents for neuromuscular blockers (e.g. rocuronium and vecuronium) xref , xref and drugs of abuse such as methamphetamine. xref Host Tet1 has displayed excellent biocompatibility according to the usual in vitro (e.g. cell death and metabolic activity, mutagenicity, lack of hERG ion channel inhibition) and in vivo (e.g. maximum tolerated dose, blood gases, blood pH, mean arterial pressure) assays. xref The group of Prof."
sparser
"M1 and related compounds display excellent biocompatibility according to both in vitro (metabolic and cell death assays; no mutagenicity by Ames test; lack of hERG ion channel inhibition) and in vivo (e.g. maximum tolerated dose; blood pH and blood gas analysis; mean arterial pressure; urinary excretion) tests. xref – xref , xref Acyclic CB[n] compounds also function as components of sensing ensembles for biologically active substances like nitrosamines and over the counter drugs. xref Given the high affinity of (acyclic) CB[n]-type receptors toward their guests, we envisioned they could also be used as in vivo reversal agents for appropriate targets similar to the use of Sugammadex to reverse neuromuscular block. xref Indeed, we found that acyclic CB[n] dose dependently reversed the in vivo biological effect of the neuromuscular blockers rocuronium, vecuronium, and cisatracurium as well as the depth of anesthesia after treatment with ketamine. xref – xref Conceptually related sequestration and reversal applications using macrocyclic CB[n] have been investigated in the laboratory of Prof."
sparser
"With respect to potential toxicity by hERG ion channel inhibition, 9 showed a significant increase ( P = 0.0086;
unpaired Student’s t test) in IC 50 value compared with bosutinib with IC 50 values of 3.41
and 1.01 μM, respectively, which translated into a reduced maximal
% hERG inhibition of 24 for 9 and 52 for bosutinib at
1 μM (see thefor details)."