47 results about "HERG" patented technology

Thioether-substituted benzamide compounds having the formula: are provided that exhibit exceptionally strong inhibition of Factor Xa in combination with weak hERG binding.

The present invention provides assays and kits for the screening of test compounds for their capability to induce cardiotoxicity in a subject. Said assays and kits are based on the finding that the interaction of astemizole with the HERG potassium channel can be exploited to predict cardiotoxicity of compounds during the development of new therapeutics and other agents.

Compositions and methods are provided for preventing one or more cardiac channelopathies or conditions resulting from irregularities or alterations in cardiac patterns, or both, in a human or animal subject comprising: one or more pharmacologically active agents that causes at least one of IKr channel inhibition or QT prolongation by inhibiting the activity of an ether-a-go-go-related gene (hERG); and one or more liposomes, wherein the liposomes are empty liposomes and administered prior to, concomitantly, or after administration of the pharmacologically active agent.

Provided herein are methods, compositions, and kits for the treatment of an enteric nervous system disorder. Such methods may comprise administering to a subject an effective amount of a phenothiazine compound, a peripherally restricted dopamine decarboxylase inhibitor, and / or a peripherally restricted dopamine D2 receptor antagonist that does not substantially inhibit hERG channels.

The invention discloses an application of chiral chloroquine, hydroxychloroquine or pharmaceutically acceptable salts of the chiral chloroquine and hydroxychloroquine in preparation of drugs used forpreventing and / or treating coronavirus pneumonia by using a coronavirus key drug target 3CL hydrolase (Mpro) as an action target. The chiral chloroquine and hydroxychloroquine have high bonding strength with the Mpro causing inflammation of the lung and the like; the activity of the Mpro can be significantly inhibited; and the chiral chloroquine and hydroxychloroquine are indicated to have the effect of preventing and treating pneumonia caused by coronaviruses and be able to be used as anti-pneumonia drugs. Through evaluation on the inhibitory activity of an hERG potassium ion channel, the concentration at which the chloroquine, hydroxychloroquine and enantiomers of the chloroquine and hydroxychloroquine are likely to generate cardiotoxicity to the hERG potassium ion channel is provided. The chiral chloroquine and hydroxychloroquine are prepared through chiral high-performance liquid chromatography and chiral synthesis; S-configuration chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine can be selected as a drug independently, or form a pharmaceutical composition for treating diseases caused by the coronaviruses; and due to higher activity and low cardiotoxicity of the chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine, the administration dosage range is greatly widened.

Compositions and methods are provided for preventing one or more cardiac channelopathies or conditions resulting from irregularities or alterations in cardiac patterns, or both, in a human or animal subject comprising: one or more pharmacologically active agents that causes at least one of IKr channel inhibition or QT prolongation by inhibiting the activity of an ether-a-go-go-related gene (hERG); and one or more liposomes, wherein the liposomes are empty liposomes and administered prior to, concomitantly, or after administration of the pharmacologically active agent.

The present invention provides an apparatus for evaluating a drug effect enabling on-chip evaluation of the effect of a drug while the drug is acting on hERG-expressing cells. The present invention also provides a myocardial toxicity test apparatus and method therefor enabling in vitro myocardial toxicity testing that has previously been performed in vivo. A pulsating cell population and hERG-expressing cells (target model cells) are suitably isolated and arranged on a transparent substrate so that the two form gap junctions. The hERG-expressing cells are arranged on transparent electrodes provided on the transparent substrate. The hERG-expressing cells are exposed to a flow of a liquid containing a drug such that the drug acts thereon. The difference between the normal pulsation of hERG-expressing cells and the pulsation when a drug is acting thereon is captured via electric signals obtained from electrodes, and the properties of the change in potential are evaluated.

The invention discloses a graph attention mechanism transfer learning-based small molecule drug hERG toxicity prediction method and device; the method comprises the following steps: S1, data set preprocessing: enabling a to-be-detected drug-like compound to generate a fingerprint sequence through molecular fingerprint generation software; s2, acquiring atom and chemical bond characteristics through the fingerprint sequence generated in the step S1, and constructing a molecular graph and graph characteristics through the atom and chemical bond characteristics; s3, processing the molecular map obtained in the step S2 through a map attention mechanism, and generating a feature vector of each atom in the molecule; s4, generating a molecular feature vector through a graph attention mechanism and the feature of each atom. According to the method, a molecular graph structure is processed based on a graph attention mechanism, a substructure which contributes to a predicted attribute value is effectively obtained, and a source domain data set and a target domain data set are processed based on transfer learning; and thereby, the problem that the sample size is insufficient is effectively solved.

The invention relates to a benzimidazole hERG potassium ion channel small-molecular fluorescent probe and a preparation method and applications thereof; the fluorescent probe has the structural general formula represented by the formula (I), wherein in the formula, R1 is hydroxyl, halogen, alkyl or alkoxy monosubstituent or polysubstituent, R2 is fluorophore, n is 1-6, particularly, R1 is p-halogen, and R2 is coumarin, naphthalene diimide, NBD, Cy5 or fluorescein isothiocyanate fluorophore. The invention discloses the applications of the probe in marking of hERG potassium ion channels and high-expression tumor cells or tissues, high-throughput screening of hERG potassium ion channel inhibitors, evaluation of new drug cardiotoxicity, use as a probe for identification of the hERG potassium ion channels and studies on hERG potassium ion channel physiological, pathological and related diseases.

The present invention provides compounds of general formula I, isomers thereof, non-toxic pharmaceutically acceptable salts or solvates thereof. The compounds have remarkably strengthened analgesic activity, reduce the acute toxicity obviously, have no inhibition to heart Herg channel, and reduce side effects on coordination movement of mice remarkably. The present invention realizes the separation of activity and side effects, and has a good application prospect.

The invention relates to a method for screening hERG potassium ion channel agonists and detecting toxicity. Specifically, the present invention firstly relates to a fusion protein, containing as the N-terminus of the fusion protein, between the 1-85 amino acid residues of the N-terminus of the potassium ion channel UNC-103 protein of the nematode ERG family, 75-85 amino acids in length A fragment of residue; hERG or its fragment comprising at least the S1-S6 transmembrane region and the cyclic nucleotide binding domain; and as the fusion protein C-terminal amino acid residue at position 590-829 from the C-terminus of the UNC-103 protein Between bases, a fragment of 220‑240 amino acid residues. It also relates to the polynucleotide sequence encoding the fusion protein, related transgenic nematodes, and related screening methods and applications. The present inventors constructed an in vivo screening method for the first time that can identify compounds that affect hERG intracellular transport, and screen hERG inhibitors or long QT syndrome (LQTS) related channel mutant function correctors, which are hERG toxicants. Physical detection and screening of drugs for the treatment of LQTS provides new ways and methods.

The present invention discloses a class of acetylbenzylamine piperidine amide derivatives with neuroprotective effects and applications thereof. Pharmacological experiments show that the compounds of the present invention have better protective effects on neuron cells and significant hypoxia-resistant activity in vivo. Herg test shows that the compound of the present invention has low potential cardiotoxicity and high safety. The acetylbenzylamine piperidine amide derivatives are free bases or salts of compounds with the following general chemical structure:

The invention provides a pharmaceutical pre-clinical cardiac risk assessment method. The method includes the steps of design of action potential frequency, recording of action potential, and recording of a manual patch clamp for the hERG (human ether-Alpha-go-go-related gene) channel. The method has the advantages that the risk of pharmaceutical cardiac arrhythmias is assessed by means of frequency dependence, action potential triangulation and hERG blocking dynamics, screening efficiency and accuracy of pharmaceuticals is greatly improved, and pharmaceutical clinical cardiac arrhythmias is less false positive.

The present invention provides a PY sequence short peptide and its application in inhibiting the degradation of hERG potassium channel. The sequence of the short peptide is shown in SEQ ID NO.1. The present invention also provides a derivative of the above-mentioned PY sequence short peptide, which is a chimeric peptide formed by linking the PY sequence short peptide with a cell-penetrating peptide. The cell-penetrating peptide is connected to the C-terminal or N-terminal of the short peptide of the PY sequence. The sequence of the cell penetrating peptide is shown in SEQ ID NO.2. An application of the above-mentioned PY sequence short peptide and its derivatives in inhibiting hERG potassium channel degradation. The PY sequence short peptide designed according to the binding site of Nedd4-2 and hERG channel in the present invention can significantly increase I at the level of cells and whole animals Kr This effect can significantly prevent the electrophysiological remodeling accompanied by cardiac hypertrophy, and is expected to be applied to combat arrhythmias caused by pathological cardiac hypertrophy.