IndraLab

Statements

KCN inhibits KCNH2. 59 / 59
| 3 56
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"The hERG potassium channel inhibition predicts the rate of cardiotoxicity of any drug."
39215267
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"However, medium risk for human ether-a-go-go-related gene (hERG) potassium channel inhibition was predicted."
| PMC
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"Screening of drug candidates for hERG potassium channel inhibition has become an early step in testing for potential drug dependent long QT syndrome that is linked to sudden death [ xref ]."
29340047
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"GSK693 did not show any sign of cytotoxicty and no hERG potassium channel inhibition ( xref ), suggesting a low risk for general toxicity and cardiotoxicity."
27428438
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"Subsequently, the head group substituent exploration showed that the methoxy group in the ortho-position of the carboxylic acid was beneficial to the potency and yielded the optimal compound 23 with s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38070432
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"With a longer link group (n ≥ 3), the triazole group of the drug would be impacted by solvent effect and shift the “barycenter” to the solvent region, which was detrimental to a stable drug-protein co[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31387063
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"The AMES toxicity, hepatotoxicity, hERG potassium channel inhibition and skin sensitization parameters were predicted to find out the toxicity profile of the identified phytochemical constituents from the E. sativa crude extract."
35209197
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"The toxicity profile of the phytochemical elements discovered in P. lentiscus EO and decoction was projected using the toxicity criteria of AMES, hERG potassium channel inhibition, skin sensitization, hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity."
37760813
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"The ADMETlab web server was also used to predict the following: (1) absorption—CaCO 3 permeability (CaCO 2 ), P-gp inhibitor/substrate (P-gp), human intestinal absorption (HIA), 20% bioavailability (F20%), and 30% bioavailability (F30%)); (2) distribution—plasma protein binding (PPB), blood–brain barrier (BBB), and volume distribution (VD); (3) metabolism—CYP inhibition and substrate; (4) excretion—half-life (T 1/2 ) and clearance (CI) and; (5) toxicity—the hERG potassium channel inhibition (cardiotoxicity), H-HT (human hepatotoxicity), AMES (Ames mutagenicity) and SkinSen (skin sensitization), among others."
38132819
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"Furthermore, the predicted toxicity profile revealed that ZDS20 showed no risk in hERG potassium channel inhibition, mutagenic response, respiratory sensitisation, and irritation for eye ( xref ), irrespective of risk in carcinogencity and DILI (drug induced liver injury)."
38887057
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"The authors demonstrated a high vulnerability to tachycardia of tachypaced hiPS-CMs, terminated by ryanodine receptor stabilization or sodium or hERG potassium channel inhibition, hence indicating this new model as a potential tool to test anti-arrhythmic drugs to treat ventricular tachycardia [ xref ]."
32403456
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"Lastly, early safety assessments done across different enzymatic assays indicated that GSK-693 did not show any sign of cytotoxicity and no hERG potassium channel inhibition [ xref ], suggesting a low risk for general toxicity and cardiotoxicity observed in isoniazid."
34068171
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"Rubi et al. [ xref ] concluded that ibogaine prolongs repolarization through human ether-a-go-go-related gene (hERG) potassium channel inhibition."
39081435
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"The calculated estimation of the likelihood of the hERG potassium channel inhibition (hERGfilter) and the pIC 50 as a measure of affinity for hERG K + channel (hERGpIC 50 ) is promising for all compou[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38582487
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"Highly basic functional groups not only hamper permeability (which may lead to poor absorption), but may also lead to safety issues such as hERG potassium channel inhibition, CYP enzyme inhibition and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29494843
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"However, assessing a hERG potassium channel inhibition, CYP inhibition and A549 cell growth reduction showed liabilities of the most active inhibitors of T. brucei bloodstream forms as the result of h[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38643671
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"This finding indicated no substantial change in hERG potassium channel inactivation after the administration of 2 μM of osimertinib."
37324483
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"The in silico toxicological evaluation indicates a good profile for both compounds 5c and 5d , in which present a low qualitative estimation of causing any phospholipidosis, mutagenesis, reproductive [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30528164
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"The toxicity profile of all the identified phytoconstituents from S. repanda ethanolic crude extract has been predicted based on AMES toxicity, hepatotoxicity, hERG potassium channel inhibition and skin sensitization parameters."
33540783
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"To assess hERG potassium channel inhibition, we utilized the FLIPR® Potassium Assay, a commercially available kit."
39845806
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"Properties NB-12 NB-15 NB-20 Topotecan Maximum recommended therapeutic dose administered as an oral dose (mg/kg/day) Estrogen receptor (rats) Quantitative measure of Estrogen receptor toxicity in rats Androgen receptor toxicity Quantitative measure of androgen receptor toxicity in rats Allergenic skin sensitization (mice) Allergenic respiratory sensitization in rat Fathead minnow lethal toxicity after 96 h of exposure (mg/L) Tetrahymena pyriformis growth inhibition toxicity (mmol/L) Daphnia magna (water flea) lethal toxicity after 48 h of exposure (mg/L) Bio concentration factor Biodegradation Likelihood of the hERG potassium channel inhibition in human Affinity towards hERG K+ channel and potential for cardiac toxicity (mol/L) LD50 for lethal rat acute toxicity (mg/kg) Tumorogenic dose rat (mg/kg/day) Tumorogenic dose mice (mg/kg/day) Triggering the mutagenic chromosomal aberrations Causing anemia Cardiotoxicity Neurotoxicity Nephrotoxicity Hepatotoxicity Levels of Alkaline Phosphatase Levels of GGT enzyme Levels of LDH enzyme levels of AST enzyme Levels of ALT enzyme Causing phospholipidosis Reproductive/developmental toxicity Mutagenicity (pure compound) TA97 and/or TA1537 strains of S. typhimurium TA98 strain of S. typhimurium TA100 strain of S. typhimurium S. typhimurium and/or WP2 uvrA strain of E. coli TA1535 strain of S. typhimurium Mutagenicity (microsomal rat liver TA97 and/or TA1537 strains of S. metabolites) typhimurium TA98 strain of S. typhimurium TA100 strain of S. typhimurium TA102 strain of S. typhimurium and TA1535 strain of S. typhimurium Below 3.16 Below 3.16 Below 3.16 Above 3.16 Nontoxic Nontoxic Nontoxic Toxic Nontoxic Nontoxic Nontoxic 4.3531 Nontoxic Nontoxic Toxic Toxic Nontoxic Nontoxic ."
28705120
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"The toxicity profile of sesamin has been predicted based on eye corrosion, hepatotoxicity, AMES toxicity, and hERG potassium channel inhibition."
35223101
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"The results outlined that sesamin showed toxicity only in the AMES test rather than eye corrosion, hepatotoxicity, hERG potassium channel inhibition, and T. pyriformis ."
35223101
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"Ekins S, Balakin KV, Savchuk N, et al. Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniques."
19239395
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"Highly basic functional group may lead to safety issues such as hERG potassium channel inhibition, CYP enzyme inhibition and phospholipidosis [ 34 ], we therefore replace the hydrogen at the R 2 posit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32768738
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"To examine the potential toxicity of each compound, we determined the cell viability of a hippocampal neuronal cell line (HT-22) and found that both compounds were nontoxic at a concentration of 10 μM[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34536669
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"For example, in guinea pig ventricular myocytes, dauricin, a bioactive component of Menispermum dauricum inhibited both IKs and IKr currents.20 Further examinations on the cardiac potassium channels expresssed on HEK cells showed that grape flavonoids decrease HERG channels."
35747353
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"In addition, in vitro experiments have demonstrated that the N588K mutation in hERG potassium channels decreases the sensitivity of hERG to quinidine and D-sotalol, and the corresponding IC 50 values [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23369369
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"To evaluate the risk of cardiac repolarization toxicity of hERG potassium channel inhibition by studying the compound's half inhibitory concentration (IC 50 ) on hERG current."
38224636
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"Lemme et al. developed a unique chronic tachypacing hiPSC-CM-derived EHT model with an optogenetic approach and demonstrated its effective termination using ryanodine receptor stabilization, sodium, or hERG potassium channel inhibition ( xref )."
35433691
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"KIRSCH GE, TREPAKOVA ES, BRIMECOMBE JC et al.: Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern."
17916053
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"It was observed through the study that there may not be any possibility of hERG (human Ether-a-gogo-Related Gene) potassium channel inhibition in human that means there may be no adverse cardiac effect."
28705120
reach
"The fact that this potassium channel ligand is unable to inhibit hERG (K v 11.1) currents [8,27] , made it an interesting peptide to be included in a screening for inhibitory activity on the oncogenic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27578329
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"HERG (human ether-a-go-go related gene) potassium channel inhibition (Kongsamut et al., 2002) and QT prolongation in isolated heart (Adamantidis et al., 1994) or Purkinje fibers (Drici et al., 1998) a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15289090
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"The most interesting result of this study was the very positive effect of the 3,5-dialkoxy-4-pyridyl C-unit substitution on hERG potassium channel inhibition."
30803745
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"To evaluate the possible toxicity of O. compactum and O. elongatum essential oils in terms of AMES, hepatotoxicity, hERG potassium channel inhibition, skin sensitization, and cytotoxicity, the phytochemical components of these oils were investigated ( xref )."
38668338
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"Moreover, a hERG potassium channel inhibition may induce QT interval prolongation and ventricular action potential duration (APD) prolongation associated with QT prolongation ( Vargas et al., 2015 ; Y[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30658151
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"Results of compound 1G showed no hERG (human ether-a-go-go-related gene) potassium channel inhibition in human, similar to standard drug topotecan, which otherwise may cause risk of cardiotoxicity."
29615704
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"Indeed, it is well known that hERG potassium channel inhibition results in a reduced rate of repolarization of the cardiomyocyte resulting in a prolongation of APD that can lead to a potentially life [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34678241
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"While testing for hERG potassium channel inhibition and QT prolongation has prevented torsade de pointes (TdP) inducing drugs from reaching the market, other new drugs are dropped from development, sometimes inappropriately ( xref )."
27701120
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"Whereas, virtual screenings were also performed to evaluate toxicological properties including Maximum Recommended Therapeutic Dose (MRTD), cardiac toxicity by affinity towards hERG-encoded potassium channels (described by the qualitative estimation of likelihood of the hERG potassium channel inhibition (hERG_Filter) and the pIC 50 as measure of affinity for hERG K + channel (hERG_pIC 50 )), and the hepatotoxicity (described by the level of alkaline phosphatase (AlkPhos), γ-glutamyl transferase (GGT), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH))."
35540224
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"Among the various parameters, we considered to include molecular weight (MW), logP, hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), number of rotatable bonds (RB), topological polar surface area (TPSA), ability to cross the blood-brain barrier (BBB), human intestine absorption (HIA), inhibition of P-glycoprotein (P-gp), human ether-a-go-go-related gene (hERG) potassium channel inhibition and bioavailability score (BS) as these properties play critical role (see  xref )."
36965227
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"Cardiotoxicity test of M. persimmonesis extracts was evaluated utilizing an automated patch-clamping method to measure the rate of hERG potassium channel activity inhibition in hERG-expressing HEK 293 cells."
38571591
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"In the ADMET profile, RK-59638 showed a good plasma protein binding ratio (85%), membrane permeability (29.2 × 10 –6 cm/s), in vitro toxicity (78% viability at 30 μM for HepG2 cells), and hERG potassium channel inhibition (25.4% inhibition at 10 μM)."
32478230
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"The hERG potassium channel fast inactivation is considered to be similar to the Shaker ‘C-type inactivation’ [ xref ], which consists of a collapse of the central pore; this collapse is positioned in the proximity of the selectivity filter, whose molecular arrangement is distorted, determining its inactivation [ xref , xref ]."
37110748
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"Next, we examined the hERG potassium channel inhibition of each compound at a concentration of 10 μM ( Table 6 )."
36265279
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"Here we show that clinical concentrations of psilocin do not cause significant human ether-a-go-go-related gene (hERG) potassium channel inhibition, a major risk factor for adverse cardiac events."
34871422
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"The calculated qualitative parameters of the likelihood of the hERG potassium channel inhibition as hERG_filter and the pIC 50 as a measure of affinity for hERG K + channel (hERG_pIC 50 ) are promising for compounds 1–3 and new 7–9 i.e. they can be classified as non-cardiotoxic."
35540224
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"KIRSCH GE, TREPAKOVA ES, BRIMECOMBE JC et al.: Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern."
17298291
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"Deletion of protein kinase A phosphorylation sites in the HERG potassium channel inhibits activation shift by protein kinase A. J Biol Chem 274:27,457–27,462."
11282297
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"Further biological evaluation revealed that it did not show obvious cytotoxicity and hERG potassium channel inhibition at micromolar concentration."
26479744
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"Before moving forward to in vivo studies, toxicity profile of some compounds was investigated by evaluating the ether-a-go-go-related gene (hERG) potassium channel and cytochrome P450 inhibition."
33081988
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"Also, the drug carries a reported risk for QT-interval prolongation most commonly caused by hERG potassium channel inhibition."
35586063
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"Meanwhile, 67a has no significant cytotoxicity and hERG potassium channel inhibition at micromolar concentration."
34023737
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"The current regulatory paradigm to mitigate this risk involves both patch-clamp analysis of exogenously expressed human ether-a-go-go related gene (hERG, I Kr ) potassium channel inhibition and testin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29155283
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"Further evaluation of the lead compounds in terms of various ADMET properties such as hERG potassium channel inhibition, mutagenicity, induction/inhibition of CYP450 isoforms, metabolic stability/half-life, permeability, will provide useful data for advancing those compounds."
35462232
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"Thus, a fluorescence polarization assay was carried out to determine the potential hERG potassium channel inhibition of 22 in comparison with lead compound 1 and the references HF and LUM ( xref )."
33666415
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"To assess hERG potassium channel inhibition caused by 4-AcO-DET and 4-HO-MET, the hERG assay was performed according to a previously described method ( Yoon et al., 2019a , b )."
31706004
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"We have subjected the compounds to preliminary cytotoxicity studies on human HUVEC and HepG2 cell lines and determined their hERG (human ether-a-go-go-related gene) potassium channel inhibition (Supplementary Table  xref )."
33420011