34 results about "Potassium channel" patented technology

The present invention relates to a polysubstituted aryl derivative, a preparation method therefor, and the use of a pharmaceutical composition containing the derivative in medicine. Specifically, the present invention relates to a polysubstituted aryl derivative as shown in general formula (I), a preparation method therefor, a pharmaceutically acceptable salt thereof, and the use thereof as a therapeutic agent, in particular as a Kv1.3 potassium ion channel inhibitor, wherein the definition of each substituent in general formula (I) is the same as defined in the description.

The invention discloses a KCR1 mutant suitable for plant potassium ion steady state regulation and application thereof, and relates to the technical field of bioengineering, and the KCR1 mutant at least has T136A and G140A mutations on the basis of light-operated potassium ion channel protein KCR1. The invention also discloses a gene for coding the KCR1 mutant. The invention also discloses application of the KCR1 mutant or gene in plant culture, cultivation of new plant varieties or preparation of plant culture products. The KCR1 mutant disclosed by the invention has a blue-shift excitation spectrum compared with a wild type, can realize accurate regulation and control of plant potassium ion flow through illumination regulation and control, and has a relatively great application value in the aspects of light-controlled plant cultivation, plant potassium ion channel research and the like.

The invention relates to potassium ion channel inhibitor compounds having improved affinity and selectivity for Kv1.3 ion channel, and enhanced stability. The inhibitor compounds comprise a polypeptide component which is a miniprotein. The invention also relates to therapeutic indications and diagnostic uses of the inhibitor compounds.

The invention discloses a non-sterilization type mildew-proof and antibacterial material capable of dynamically responding to thallus proliferation as well as a preparation method and application of the non-sterilization type mildew-proof and antibacterial material. The material comprises polyvinyl alcohol, carboxymethyl cellulose or a salt thereof and metal ions, and the polyvinyl alcohol, the carboxymethyl cellulose or the salt thereof are bridged through the metal ions; the metal ions comprise Li < + >. The material disclosed by the invention takes Na < + > released by thallus proliferation as a signal medium, releases Li < + > as required through a coordination-dissociation process, and further induces thallus cells to actively ingest Li < + > through metabolic deception of occupying a potassium ion channel by utilizing a hydration radius of Li < + > similar to K < + > according to the metabolic demand of sodium excretion and potassium ingestion in the thallus proliferation process; on one hand, bacterial cell replication lacks essential nutrient substance K < + >, and finally gradually declines; on the other hand, protein space conformation is changed and inactivated by capturing water molecules of intracellular protein, and the two aspects have a synergistic effect, so that the efficient mildew-proof and antibacterial effects of Li < + > at low concentration can be realized, and the effect is lasting.

The invention provides a mechanical and pH dual-regulated butterfly potassium ion channel molecule as well as a preparation method and application thereof, and belongs to the technical field of biomimetic materials. According to the butterfly-shaped potassium ion channel molecule disclosed by the invention, third-generation and fourth-generation dendrimer polypropyleneimine (POPAM) are respectively taken as a core, and POPAM is connected with an ion binding site benzo-21-crown ether-7 through a urea bond. Intramolecular hydrogen bond constraint enables GnC7 to present a symmetrical butterfly-shaped topology structure, and the channel has unique motion characteristics, and finally, efficient potassium ion transmembrane transmission with highest potassium-sodium selectivity up to now is realized. The dynamic characteristic is used as the core attribute of GnC7, so that the channel can adjust the potassium ion transmission rate according to the membrane tension change caused by mechanical force. Meanwhile, benzylamine hexafluorophosphate Bh influenced by pH is used as a blocking agent of GnC7 through a host-guest specific compounding effect, and switching of pH-regulated potassium ion transmission can be realized.

The application discloses a KCR1 mutant suitable for plant potassium ion homeostasis regulation and application thereof, relates to the technical field of bioengineering, and the KCR1 mutant has at least T136A and G140A mutations on the basis of a light-controlled potassium ion channel protein KCR1. The application also discloses a gene encoding the KCR1 mutant. The application also discloses application of the KCR1 mutant or the gene in plant culture, breeding of new plant varieties or preparation of plant culture products. The KCR1 mutant has a blue-shifted excitation spectrum compared with a wild type, and can realize precise regulation of plant potassium ion flow through light regulation, and has great application value in light-controlled plant breeding and research of plant potassium ion channels.

This invention discloses US The application and methods of genes in regulating rice plant height, grain length, grain width, and grain weight belong to the field of crop genetics and breeding technology. This invention reveals for the first time the potassium ion channel protein gene. US This gene has a pleiotropic function in rice, regulating plant height, grain length, grain width, and grain weight. By silencing or knocking out this gene, rice plant height can be significantly reduced, lodging resistance can be enhanced, and grain length, grain width, and thousand-grain weight can be greatly increased. This overcomes the adverse effect of traditional dwarfing genes often being accompanied by smaller grains, achieving synergistic improvement in dwarfing and grain weight. The discovery of this gene provides a brand-new gene resource and an efficient molecular breeding target for high-yield, high-quality, and lodging-resistant rice breeding, and has important theoretical value and broad application prospects.

The invention belongs to the technical field of genetic engineering, and relates to a gene for regulating and controlling the potassium content of tobacco leaves, in particular to a tobacco potassium ion channel NtAKT1 gene and application thereof. The gene is a potassium ion channel, and the base sequence of the gene is as shown in SEQ ID NO. 1; wherein nucleotides from the 112th site to the 413th site are specific nucleic acid fragments. According to the invention, real-time PCR (polymerase chain reaction) shows that the gene has the highest expression quantity at the root of the tobacco. After a gene transient silencing technology (VIGS) or NtAKT1 gene knockout, the potassium ion content of tobacco leaves is remarkably reduced compared with that of a control group. According to the invention, the transport function of the NtAKT1 gene on the potassium content of the tobacco leaves is defined, a new evidence is provided for analyzing a molecular regulation mechanism of the potassium ion content of the tobacco leaves, a new thought is provided for regulating and cultivating high-potassium-content tobacco leaves through gene expression, and a new gene resource is provided for improving the potassium content of the tobacco leaves through a molecular means.

The present invention discloses an agonist of a TREK-1 potassium ion channel and its application in analgesic therapy. Specifically, the present invention discloses a compound that can activate the TREK-1 potassium ion channel, the compound has a significant analgesic effect, and can be used to prepare a pharmaceutical composition and preparation for preventing and / or treating chronic pain (muscle and soft tissue pain, bone and joint pain, headache, visceral pain, pathological neuralgia), acute pain, and cancer pain.

The invention provides a compound (I) or pharmaceutically acceptable salts and esters thereof, and a pharmaceutical composition containing the compound, and also provides application of the compound as a potassium ion channel regulator, application of the compound in preparation of drugs for potassium ion channel related diseases, and a corresponding pharmaceutical composition.

Disclosed is a compound of formula (I), wherein all symbols are defined in the description. Also disclosed are pharmaceutical compositions comprising the compounds, methods of making the compounds, kits comprising the compounds and methods of using the compounds to prevent and / or treat disorders associated with dysregulation of TREK-1, TREK-2 or both TREK-1 and TREK-2 in a mammal.

The invention relates to a polysubstituted aryl derivative, a preparation method of the polysubstituted aryl derivative and application of a pharmaceutical composition containing the polysubstituted aryl derivative in medicine. Specifically, the invention relates to a polysubstituted aryl derivative as shown in a general formula (I), a preparation method and a medicinal salt thereof, and application of the polysubstituted aryl derivative as a therapeutic agent, especially as a Kv1.3 potassium channel inhibitor, and definition of each substituent in the general formula (I) is the same as that in the specification.

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a Kv7 potassium ion channel opener as well as a preparation method and application thereof. The method comprises the following steps: adding a compound 1, a compound 2 and triethylamine into ethyl acetate, and carrying out a first reaction to obtain a reaction solution; performing extraction, water washing, drying and vacuum concentration on the reaction liquid, and then adding the reaction liquid into a mixed solution of a sodium hydroxide aqueous solution and isopropanol to perform a second reaction to obtain a compound 3; adding the compound 3, a catalyst and NH4HCO2 into the mixed solvent, and carrying out amination reaction to obtain a compound 4; and adding the compound 4, the compound 5 and triethylamine into ethyl acetate for reaction to obtain the Kv7 potassium ion channel opener. The metabolic stability and the structural rigidity are improved.

A compound of formula Iwherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

The invention discloses a synergistic composition containing isoxazoline insecticidal and acaricide, which is composed of a compound I and a compound II, the compound I is CCXN-15-005-S (S configuration) or an agrochemically acceptable salt thereof, and the compound II is CCXN-15-005-S (S configuration) or an agrochemically acceptable salt thereof. The compound II is selected from any one of a nicotinic acetylcholine receptor agonist, a chordinal TRPV channel regulator, an acetyl-coenzyme A carboxylase (ACCase) inhibitor, a mitochondrial electron transfer inhibitor, a calcium-activated potassium ion channel regulator and trifluoroethyl thioether (sulfoxide) or an agrochemically acceptable salt thereof. The synergistic composition can be used for preventing and treating pests and harmful mites of thysanoptera, hemiptera and acarus and has a wider agricultural application prospect.

The invention relates to a kit for detecting heart potassium ion channel coding gene idiopathic ventricular fibrillation risk gene SNP (Single Nucleotide Polymorphism) loci, which comprises 38 pairs of specific multiplex PCR (Polymerase Chain Reaction) primer pairs with 41 required SNP loci, 41 SNP single-base extension primers, and necessary PCR reaction liquid, SNaPshot reaction liquid, shrimp alkaline phosphatase and exonuclease I. The kit is used for detecting heart potassium ion channel coding gene idiopathic ventricular fibrillation risk gene SNP loci. According to the kit, the multiple PCR technology, the SNaPshot micro-sequencing technology and the capillary electrophoresis technology are combined to screen the risk gene SNP sites related to the idiopathic ventricular fibrillation on the heart potassium ion channel coding genes, the SNP related to the idiopathic ventricular fibrillation on 41 potassium ion channel genes can be detected only through one experiment, a clear conclusion can be obtained, and result interpretation is simple and objective.

Disclosed is a compound of formula (I): Also disclosed are pharmaceutical compositions comprising the compound, methods of making the compound, kits comprising the compound and method of using the compound to prevent and / or treat disorders associated with dysregulation of TREK-1, TREK-2 or both TREK-1 and TREK-2 in a mammal.

The present application relates to a method for inhibiting neuronal hyperexcitability via AAV-mediated expression of a potassium channel. The present application relates to a recombinant adeno-associated virus vector (rAAV vector) for inhibiting neuronal hyperexcitability. The rAAV vector comprises a nucleotide sequence encoding a potassium channel. Further, the present application also relates to a virus particle comprising the rAAA vector, a pharmaceutical composition comprising the rAAA vector and / or the virus particle, and a use thereof in the preparation of a drug for treating diseases related to neuronal hyperexcitability.

The present invention provides a butterfly-shaped potassium ion channel molecule and its preparation method and application for mechanical and pH dual regulation, belonging to the field of biomimetic material technology. The butterfly-shaped potassium ion channel molecule of the present invention is respectively based on three-generation and four-generation dendrimer polypropylene imine (POPAM), and POPAM and ion binding site benzo-21-crown ether-7 are connected with urea bonds. Intramolecular hydrogen bond constraint causes GnC7 to present a symmetrical "butterfly-shaped" topological structure, and the channel has unique motion characteristics, and ultimately achieves efficient and so far the highest potassium-sodium selectivity across the membrane transport of potassium ions. Dynamic characteristics, as the core attribute of GnC7, enable the channel to regulate potassium ion transmission rate according to the membrane tension changes caused by mechanical force. Meanwhile, benzylamine hexafluorophosphate Bh, which is affected by pH, acts as a blocker of GnC7 through host-guest specific composite action, which can realize the switch for pH regulation potassium ion transmission.

This invention discloses a traditional Chinese medicine composition for regulating calcium ion homeostasis in the stomach, belonging to the field of traditional Chinese medicine technology. It is made from calcined oyster shell, calcined abalone shell, dried plum, poria cocos, and jujube seed in a specific weight ratio. This invention selects highly efficient calcium sources, calcined oyster shell and calcined abalone shell, in equal proportions, avoiding the deficiency of insufficient calcium content in traditional calcined dragon bone. It targets and supplements local calcium ions in the stomach, enhances the stabilizing effect of calcium ions on potassium ion channels, inhibits abnormal potassium ion leakage, and improves gastrointestinal smooth muscle tone. At the same time, it eliminates unsuitable medicinal materials such as Codonopsis pilosula, Astragalus membranaceus, Eucommia ulmoides, and Lycium barbarum. It uses Prunus mume to inhibit the proliferation of harmful bacteria in the small intestine and reduce fermentation and gas production, Poria cocos to supplement gastrointestinal trace elements, and Ziziphus jujuba var. spinosa to stabilize potassium ion channels, restore the calcium-potassium ion balance in the stomach, improve gastrointestinal motility rhythm, and alleviate problems such as small intestinal bacterial overgrowth, insufficient gastrointestinal motility, and abdominal distension. This composition does not contain sucrose, maltodextrin, chemical additives, or irritating excipients. It is fully decocted and suitable for people with fragile gastrointestinal barriers and immune sensitivity. The raw materials are safe and readily available, the preparation method is simple, and it has broad application prospects in gastrointestinal conditioning.

The application discloses an antiepileptic preparation preparation method and application of a micro ribonucleic acid 145b targeting agent, and relates to the technical field of biological medicine. The method comprises the following steps: constructing a neuron-specific recombinant adeno-associated virus plasmid vector, wherein the vector comprises a neuron-specific promoter hSyn, a reporter gene, an enhancer, and a functional nucleic acid sequence for targeting and inhibiting micro ribonucleic acid 145b; using an adeno-associated virus packaging system to transfect the vector to a packaging cell for virus packaging; collecting a lysis solution and separating out a recombinant adeno-associated virus particle through a purification process; and resuspending the virus particle to obtain a preparation. The application specifically down-regulates the miR-145b level in hippocampal neurons, releases the inhibition of the Kcnq3 potassium ion channel, further up-regulates the Kcnq3 expression, restores the M current, and reduces the neuron excitability from a molecular mechanism.

The present invention discloses a compound with endoplasmic reticulum targeting and its application. The compound has the following chemical formula: #imgabs0# The compound provided by the present invention has good endoplasmic reticulum targeting and the ability to induce the production of type I reactive oxygen species. In addition, the compound can induce time-dependent depletion of endoplasmic reticulum calcium in cancer cells under light conditions. More importantly, the existing anti-diabetic drug glibenclamide closes the ATP-dependent potassium ion channel (K) on the endoplasmic reticulum membrane. + ATP ), the compound-induced loss of endoplasmic reticulum calcium into the cytoplasm will lead to severe depolarization of the endoplasmic reticulum membrane potential, and ultimately activate the downstream endoplasmic reticulum and mitochondria-dependent apoptosis pathways, leading to cancer cell death, while also embodying the new use of glibenclamide.

Disclosed is a compound of formula (I), wherein all symbols are defined in the description. Also disclosed are pharmaceutical compositions comprising the compounds, methods of making the compounds, kits comprising the compounds and methods of using the compounds to prevent and / or treat disorders associated with dysregulation of TREK-1, TREK-2 or both TREK-1 and TREK-2 in a mammal.

The present invention relates to a 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole derivative, a preparation method therefor, and a medical use of a pharmaceutical composition containing the derivative. Specifically, the present invention relates to a 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole derivative as shown in general formula (I), a preparation method therefor, and a pharmaceutically acceptable salt thereof, as well as a use thereof as a therapeutic agent, particularly as a Kv1.3 potassium channel inhibitor. The definitions of the substituents in general formula (I) are the same as those defined in the description.

The present invention addresses the problem of providing a new ischemic disease treatment strategy targeting pericytes. As a solution, the present invention provides an inflammation suppressant or a tissue protective agent for ischemic injury, each including an inhibitor which blocks ATP-sensitive potassium (KATP) channels present in a pericyte. In particular, the KATP channel is composed of pore-forming KIR6.1 and regulatory SUR2 subunits, and it is preferable for the inhibitor to act on the KIR6.1. The inflammation suppressant or the tissue protective agent for ischemic injury is preferably used in the treatment of ischemic diseases such as cerebral infarction or ischemic cardiac disease.

The present invention belongs to the technical field of heterocyclic compounds, and particularly relates to a Kv7 potassium ion channel opener, a preparation method thereof and an application thereof. Compound 1, compound 2 and triethylamine are added to ethyl acetate for a first reaction to obtain a reaction solution; the reaction solution is subjected to extraction, washing with water, drying, and concentration under reduced pressure, and then added to a mixed solution of an aqueous sodium hydroxide solution and isopropanol for a second reaction to obtain compound 3; compound 3, a catalyst and NH4HCO2 are added to a mixed solvent for an amination reaction to obtain compound 4; compound 4, compound 5 and triethylamine are added to ethyl acetate for a reaction to obtain a Kv7 potassium ion channel opener. The present invention improves the metabolic stability and the rigidity of the structure.

The invention belongs to the technical field of biomedicine, and particularly relates to a KV1.3 expression vector, a cell-free expression system, a recombination channel and application thereof. The recombinant expression vector is obtained by inserting a DNA (deoxyribonucleic acid) sequence as shown in SEQ ID NO.1 between an Nde I site and an Xho I site of a pIVEX-2. 4d vector, and the recombinant expression vector is named as pIVEX-K. The cell-free expression system is obtained by transferring the expression vector into a cell-free system. The recombination channel is obtained by recombining a cell-free expression system product and lipidosome. The recombinant channel can be applied to high-throughput screening of compounds influencing the potassium ion channel function, the influence of the compounds on the potassium channel function is directly displayed by monitoring the change of a fluorescence signal before and after a to-be-detected object is added, and the recombinant channel has the characteristics of simplicity in operation, short test period and high sensitivity.

The present invention provides the following compound (I) or a pharmaceutically acceptable salt and ester thereof, and a pharmaceutical composition comprising the compound of the present invention. The present invention further provides a use of the compound of the present invention as a potassium ion channel modulator, a use of the compound in the preparation of a drug for diseases related to potassium ion channels, and a corresponding pharmaceutical composition.

The present application discloses a garlic stomatal opening potassium ion channel AsKAT1 molecule and its application. The nucleotide sequence and amino acid sequence of the AsKAT1 molecule are shown in SEQ ID NO.3 and SEQ ID NO.4, respectively. The gene is mainly expressed in stomatal guard cells. The present application constructs an animal expression vector containing the above gene AsKAT1, proves that the gene protein has the transport activity of mediating the inward absorption of potassium ions, and finds its regulatory mechanism: the potassium absorption activity of AsKAT1 is promoted by extracellular high potassium and low pH, and then the mechanism is applied to the stomatal regulation of garlic leaves in the field, which effectively promotes the opening of stomatal pores, thereby enhancing the photosynthetic efficiency and increasing the garlic yield.

The invention belongs to the technical field of biological medicine, and particularly relates to preparation of a novel high-selectivity KV7.2 opener and application of the novel high-selectivity KV7.2 opener in antiepileptic drugs. A series of KV7.2-targeted small-molecule inhibitors are designed and synthesized, and the small-molecule inhibitors can enhance the current of a potassium ion channel KV7.2, accelerate channel activation and delay the inactivation process of the channel. The small molecule has a remarkable potential for treating epilepsy, shows efficient anti-epileptic activity in three classic epilepsy models for simulating human comprehensive attack and drug-refractory focal attack, is remarkably superior to positive control RTG, can be used for preparing anti-epileptic drugs and has a wide application prospect.