58 results about "Ion channel activity" patented technology

The invention provides nanosensors and nanosensor components for the detection of ion channel activity, receptor activity, or protein protein interactions. Certain of the nanosensor components comprise a nanoparticle and recognition domain. Following contact with cells and, optionally, internalization of the nanosensor component by a cell, the recognition domain binds to a target domain, e.g., a heterologous target domain, of a polypeptide of interest such as an ion channel subunit, G protein coupled receptor (GPCR), or G protein subunit. Ion channel activity, GPCR activity, or altered protein interaction results in a detectable signal. The nanoparticles may be functionalized so that they respond to the presence of an ion by altering their proximity. Certain of the nanosensors utilize the phenomenon of plasmon resonance to produce a signal while others utilize magnetic properties, RET, and / or ion-sensitive moieties. Also provided are polypeptides, e.g., ion channel subunits, comprising a heterologous target domain, and cell lines that express the polypeptides. Further provided are a variety of methods for detecting ion channel activity, receptor activity, or protein interaction and for identifying compounds that modulate one or more of these. In certain embodiments the invention allows the user to detect the activity of specific ion channels even in the presence of other channels that permit passage of the same ion(s) or result in activation of the same downstream targets, thereby achieving improved specificity in high throughput screens while at the same time providing a high signal to noise ratio.

The present invention relates to compounds that interact with ion channels. In particular, the invention relates to compounds having the structural Formula (I), (II), (III) or (IV), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or a pharmaceutically acceptable salt and / or solvate thereof, Formula (I), (II), (III), (IV), wherein X1, X2, Y, Z, W, R1, R8, R9, R10, L, A, z, and n have the meaning defined in claim 1. The invention also relates to methods for preparing said compounds, to pharmaceutical compositions comprising said compounds, and to the use of said compounds in methods for treatment of the human and animal body.

A method to prepare viruses lacking ion channel activity is provided.

The invention pertains generally to the field of drug discovery science. More specifically, the invention refers to a drug screening assay and device that is used to test the effect of specific chemical compounds as use dependent ion channel blockers. The invention includes a unique method for stimulating cells with photoconductive stimulation and reading consequent cell ion channel activity with the optical imaging of fluorescent dyes.

A method to prepare viruses lacking ion channel activity is provided.

Urea derivatives which comprise piperidine or piperazine rings and further substitution are effective in ameliorating conditions characterized by unwanted calcium ion channel activity.

Methods of using imidazo[1,2-α]pyridine ether compounds for modulating ion channel activity in a warm-blooded animal are disclosed.

This invention provides novel methods and compositions for treating and preventing seizures by administration of ASIC1a receptor activating compounds. A novel method of assaying ASIC1a receptor activating compounds is included in the present invention. According to the invention applicants have demonstrated that seizure duration, intensity, and progression may be modulated by administration of an ASIC1a receptor activator which acts to increase the endogenous activity of ASIC1a receptors to mediate the effects of low pH in the CNS. The inventors have also found that the ASIC1a receptor activator may prevent such seizures altogether.

The present invention provides compositions and methods for the manipulation of ion channels. For example, the present invention relates to Parkinson's and other neurological diseases and conditions, and treatments thereof. In particular, the present invention provides methods of decreasing pathophysiological high frequency neuronal bursts of Parkinson's and other neurological diseases and conditions. Methods of the present invention comprise decreasing Kv3 ion channel activity in fast-spiking neurons, including by decreasing activity of a Kv3.4 protein and by specifically targeting a Kv3.4 protein with an inhibitor.

Aromatic derivatives of aliphatic diamines are effective in ameliorating conditions characterized by unwanted calcium ion channel activity, especially T-type and N-type channels. These conditions include, for example, stroke and pain.

The present invention relates to compounds that interact with ion channels. In particular, the invention relates to compounds having the structural Formula (I), (II), (III) or (IV), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or a pharmaceutically acceptable salt and / or solvate thereof, Formula (I), (II), (III), (IV), wherein X<1>, X<2>, Y, Z, W, R<1>, R<8> , R<9>, R<10>, L, A, z, and n have the meaning defined in claim 1. The invention also relates to methods for preparing said compounds, to pharmaceutical compositions comprising said compounds, and to the use of said compounds in methods for treatment of the human and animal body.

Derivatives of urea that contain piperazine rings and additional substitution with aromatic groups are effective in ameliorating conditions associated with unwanted calcium ion channel activity.

Aromatic derivatives of aliphatic diamines are effective in ameliorating conditions characterized by unwanted calcium ion channel activity, especially T-type and N-type channels. These conditions include, for example, stroke and pain.

The present invention discloses a method of employing ion channel active compounds to deliver metabolism-enhancing molecules within the cell to promote rapid wound healing. It also develops a delivery kit for meperidine as a local anesthetic and wound healing accelerant for dental surgical use. And meperidine thus serves as a pattern for future design of novel wound healing compounds.

This invention relates to the use of compounds capable of inhibiting the activity of a proton-gated cation channel in the treatment of alleviation of diseases or disorders associated with, or mediated by a drop in extra cellular pH.

Materials, methods and a computer system are provided which facilitate the identification and characterization of modulators of potassium ion channels, particularly the HERG channel.

The present invention relates to methods for detecting the activity of an ion channel in a cell. The methods comprise providing a loading buffer solution to a cell that has an ion channel. The loading buffer comprises at least one thallium indicator (e.g., an environmentally sensitive, luminescent dye) and a physiological concentration of chloride ions. The methods further comprise providing a stimulus buffer to the cell, wherein the stimulus buffer comprises thallium (e.g., thallium ions). Providing the stimulus buffer causes thallium influx into the cell through the ion channel. After providing the stimulus buffer, the luminescence (e.g., fluorescence) of the dye in the cell is detected. The luminescence of the dye can change in the presence or absence of thallium. The methods may be used to measure influx or efflux of thallium through an ion channel.

N-diarylaminoalkyl-substituted piperazine / 4-aminopiperidine compounds of formula (1) are disclosed, wherein each of A and B is independently a 6-membered aromatic or nonaromatic, carbocyclic or heterocyclic moiety or is an aminoalkyl and wherein one and only one of A and B may be H or alkyl (1-8C) or wherein A and B together form an optionally substituted 6-membered aromatic of nonaromatic, carbocyclic or heterocyclic moiety; R<1> is H or alkyl (1-8C), Z is N or CHNR<2> wherein R<2> is H or alkyl (1-8C), X is straight chain alkylene (1-4C) wherein optionally at least one carbon adjacent to a nitrogen is in the form of C=0; each R<3> is an independent substituent; n=0-2; Ar is a six-membered aromatic or heteroaromatic ring; wherein each cyclic moiety included in A or B each Ar moiety in formula (1) may be substituted by one or more substituents. These compounds and salts or conjugated thereof are able to block N-type and T-type calcium channels and are useful for treating conditions mediated by calcium ion channel activity such as chronic pain.

A patch-clamp system employs a high-frequency characterization of cell wall membranes. Changes in the frequency response of a tank circuit incorporating the cell wall membrane impedance provides highly sensitive and highly time-resolved measurements of ion channel activity.

A patch-clamp system employs a high-frequency characterization of cell wall membranes. Changes in the frequency response of a tank circuit incorporating the cell wall membrane impedance provides highly sensitive and highly time-resolved measurements of ion channel activity.

Compositions and methods for detecting the activity of an ion channel in a cell are described. The methods include providing a loading buffer solution to the cell, where the loading buffer includes athallium ion indicator and optionally chloride ions, and providing a stimulus buffer that includes thallium ions to the cell. Providing the stimulus buffer can cause thallium ion influx into or effluxout of the cell through the ion channel. After providing the stimulus buffer, a change in at least one optical property of the thallium ion indicator is detected in response to thallium influx or efflux, thereby detecting the activity of the ion channel.

The invention relates to field of medical design, medical chemistry and pharmaceutics. The invention intends to find out molecule that can activate or prevent potassium ion channel activity by employing computer on the basis of crystal three-dimensional structure of potassium ion channel, then derivatives sifted compound and provides N, N'- disubstituted piperazine derivatives and its salt accepted by pharmacy. The construction formula of said derivatives is expressed in following graph. The invention also relates to the method for preparing said derivatives and its salt and their application. Said compound can be used as activating agent or preventing agent for potassium ion channel, and the potassium ion can be selectively shifted in or out cell by activating or preventing the activity of potassium ion channel. The compound mentioned in this invention can be used to treat and / or prevent cranial vascular disease relevant to physiological pathological and pharmacologia of cardiovascular system effectively.

This invention relates to the use of compounds capable of inhibiting the activity of a proton-gated cation channel in the treatment of alleviation of diseases or disorders associated with, or mediated by a drop in extra cellular pH.

Compositions and methods for protecting neuronal cells from pressure-induced apoptotic cell death which comprises administering to a subject in need of such treatment at least one compound which directly or indirectly inhibits the activity of an ion channel on neuronal cells and thereby inhibits the effect of pressure on the cells.

Screening assays and methods of employing the screening assays designed to identify potential inhibitors of amyloidal neurodegenerative disease. The screening assays comprises providing a membrane construct disposed on a substrate and contacting the membrane construct with Aβ peptide capable of forming an Aβ peptide ion channel in the construct. The membrane construct is then contacted with a test compound. Aβ peptide ion channel activity is determined after the construct has incubated with the Aβ peptide in the presence and in the absence of the test compound. A reduction in the Aβ peptide ion channel activity of the membrane construct contacted with the test compound in comparison to a different membrane construct contacted with the same Aβ peptide in the absence of said test compound indicates that the test compound is an inhibitor of amyloidal neurodegenerative disease.

The invention discloses an infectious bronchitis recombinant virus lack of E protein ion channel activity as well as a preparation method and application. A 26-site amino acid of a protein E of a wildinfectious bronchitis recombinant virus is mutated from aminopropionic acid to phenylalanine to obtain the infectious bronchitis recombinant virus lack of the E protein ion channel activity. By constructing the infectious bronchitis recombinant virus lack of the E protein ion channel activity and obtaining a mutant as well as by virtue of a separation purification method for the mutated virus andthe characteristic analysis of the mutated virus, the development of specific antiviral drugs and effective vaccines for preventing the virus infection can be facilitated, and the important public health and economic significance for researching corona virus can be achieved.

In vitro-differentiated retinal ganglion cells can be produced by exposing a mammalian retinal ganglion cell line to a protein kinase inhibitor. The differentiated retinal ganglion cells can be used to identify agents that protect retinal ganglion cells in vivo or in vitro from cell injury (including cell death) and agents that affect retinal ganglion cell ion channel activity.

The present invention discloses a method of employing ion channel active compounds to delivery metabolism-enhancing molecules within the cell to promote rapid wound healing. It also develops a delivery kit for meperidine as a local anesthetic and wound healing accelerant for dental surgical use. And meperidine thus serves as a pattern for future design off novel wound healing compounds.

Methods and compositions for identifying compounds which disrupt the functional interaction of an intracellular receptor region of an α-subunit of a voltage-gated ion channel and an amino-terminal inactivation region of an ion channel protein are disclosed. Compounds that disrupt the functional or binding interaction of these two regions have significant modulatory effects on ion channel activity, and thus are likely to be useful for treating and / or preventing a wide variety of diseases and pathological conditions associated with ion channel dysfunction. Such conditions include, for example, neurological disorders, cardiac diseases, metabolic diseases, tumor-driven diseases, and autoimmune diseases.