73 results about "NAV1" patented technology

The invention relates to a sodium channel regulator for inhibiting Nav1.8, and provides a compound as shown in a formula I which can be used as the sodium channel regulator for inhibiting Nav1.8, and an isomer of the compound, or a pharmaceutically acceptable salt of the compound, the invention also provides a pharmaceutical composition containing the compound and the isomer thereof, or the pharmaceutically acceptable salt thereof and a carrier or excipient, and a pharmaceutical application of the pharmaceutical composition as a NaV1.8 inhibitor (such as pain, respiratory diseases, neurological disorders, mental diseases and the like).

The present invention relates to a voltage-gated sodium channel Nav1.8 selective inhibitor and the use thereof in the preparation of a related drug. The drug is used for treating diseases responsive to the inhibition of voltage-gated sodium channel NaV1.8, such as chronic pain, enterodynia, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia. Specifically, the present invention relates to a compound as shown in formula (X), and an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof.

The present invention provides compounds useful in the treatment of conditions associated with aberrant activity of voltage gated sodium channel NaV1.8, and methods of using these compounds to treat conditions such as pain, pruritus, and cough in subjects.

The invention provides a compound as shown in a formula I which can be used as a sodium channel regulator, and a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. The invention also provides a pharmaceutical composition containing the compound and the stereoisomer, the tautomer or the pharmaceutically acceptable salt thereof and a carrier or excipient, and a pharmaceutical application of the pharmaceutical composition as a NaV1.8 inhibitor (such as pain, respiratory diseases, neurological disorders, mental diseases and the like).

Provided herein are dosing regimens and methods for treating conditions and diseases characterized by a reduced expression or function of NaV1.1 protein by modulating splicing of a pre-mRNA encoded by an SCN1A gene. The dosing regimens and methods can be used to treat Dravet Syndrome or other conditions and diseases.

Provided in the present invention are a compound as represented by formula I which can be used as a sodium channel modulator, and a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. Further provided are a pharmaceutical composition containing the compound and the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a carrier or an excipient, and the pharmaceutical use thereof as an NaV1.8 inhibitor (against, for example, pain, respiratory diseases, neurological disorders, and mental diseases).

A method and compound for regulating SCN1A gene mRNA and protein expression. Provided is a use of a guide agRNA in preparation of a drug for altering expression of a target protein in a cell of a subject. The cell has a precursor mRNA encoding the target protein, wherein the precursor mRNA comprises an intron, an exon flanking a 5' splice site of the intron, and an exon flanking a 3' splice site or a pseudo 3' splice site of the intron; the guide agRNA is capable of binding to the precursor mRNA to form a structure capable of recruiting ADAR in the cell, thereby forming a complex containing an ADAR protein; and the target protein is a Nav1.1 protein. By regulating alternative splicing of a target gene pre-mRNA, the functional RNA of the target gene and the function or expression of the target protein are affected, thereby achieving the objective of disease treatment.

The present disclosure relates to sulfonamide compounds, the use thereof for modulat-ing the sodium channel Nav1.5 and methods of treating or preventing diseases, disorders, or conditions using the same.

Provided in the present invention are a compound as represented by formula I which can be used as a sodium channel modulator, and a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof. Further provided are a pharmaceutical composition containing the compound and the stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a carrier or an excipient, and the pharmaceutical use thereof as an NaV1.8 inhibitor (against, for example, pain, respiratory diseases, neurological disorders, and mental diseases).

Provided are macrocyclic sodium channel modulators, particularly Nav1.8 channel modulators, which are compounds of Formula I, preferably Formula I1, I2, or I3, isomers, racemate, or pharmaceutically acceptable salts thereof, where the definitions of the groups and substituents are as described in the specification.

A method for regulating the mRNA and protein expression of an SCN1A gene, and a compound. Provided is a use of an antisense oligonucleotide guide RNA in the preparation of a drug for altering the expression of a target protein in a cell of a subject. The cell has a pre-mRNA encoding the target protein, wherein the pre-mRNA comprises an intron, an exon flanking a 5' splice site of the intron, and an exon flanking a 3' splice site or pseudo 3' splice site of the intron; the antisense oligonucleotide guide RNA can bind to the pre-mRNA to form a structure capable of recruiting ADAR in a cell, thereby forming a complex containing an ADAR protein; and the target protein is an Nav1.1 protein. That is, the function or expression of the functional RNA and target protein of a target gene is affected by regulating the alternative splicing of the pre-mRNA of the target gene, thereby achieving the objective of treating diseases.

The invention belongs to the technical field of biological medicines, and relates to a mutants of mu-conotoxin KIIIA rich in positive charges and application of the mutants. The mutant is obtained by implementing site-specific mutagenesis at the following positions on a mutant as shown in SEQ ID NO.1 in a sequence table: S6R; the amino acid sequence of the mutant is as shown in SEQ ID NO. 2 in a sequence table. According to the invention, systematic structural optimization is carried out on a parent peptide KIIIA containing three pairs of disulfide bonds, and a strategy of combining disulfide bond deletion and amino acid site-directed mutagenesis is adopted, so that a mutant which is simple and convenient to synthesize and has a remarkable inhibition effect on a NaV1.4 channel is obtained. The mutant has high activity, high stability and better pharmacokinetic characteristics, and has wide development potential.

The invention provides compounds that are useful for treatment of conditions associated with aberrant activity of voltage gated sodium channel Nav1.8, and methods of treating a subject with those compounds for conditions such as pain, itch, and cough.

The present disclosure relates to sulfamide (or sulfuric diamide) compounds, the use thereof for modulating the sodium channel Nav1.5 and methods of treating or preventing diseases, disorders, or conditions using the same.

This invention provides a polypeptide and its applications. The amino acid sequence of the polypeptide is shown in SEQ ID NO: 1 or SE ID NO: 2; the 12th amino acid in the amino acid sequence of the polypeptide is alanine or glutamic acid; the 19th amino acid in the amino acid sequence of the polypeptide is methionine or leucine; the 28th amino acid in the amino acid sequence of the polypeptide is lysine or isoleucine; and the 29th amino acid in the amino acid sequence of the polypeptide is selected from isoleucine, leucine, and tryptophan. The polypeptide provided by this invention has good analgesic function and can selectively inhibit the activation of Nav1.7 channels, thereby inhibiting pain, which has extremely important clinical significance for pain disorders.

Disclosed are inhibitors of voltage-gated sodium channels. More specifically, the present disclosure relates to Nav1.1 and Nav1.7 inhibitors and their use for treating or inhibiting the development of a condition in which inhibiting Nav1.1 and / or Nav1.7 activity is associated with effective treatment or inhibition, such as pain.

The present disclosure relates to sulfonamide compounds, the use thereof for modulating the sodium channel Nav1.5 and methods of treating or preventing diseases, disorders, or conditions using the same.

The application provides a polypeptide and application thereof. The amino acid sequence of the polypeptide is shown in SEQ ID NO:1 or SEQ ID NO:2; the 12th amino acid in the amino acid sequence of the polypeptide is alanine or glutamic acid; the 19th amino acid in the amino acid sequence of the polypeptide is methionine or leucine; the 28th amino acid in the amino acid sequence of the polypeptide is lysine or isoleucine; and the 29th amino acid in the amino acid sequence of the polypeptide is selected from one of isoleucine, leucine and tryptophan. The polypeptide provided by the application has good analgesic function, can selectively inhibit the activation of Nav1.7 channel, thereby inhibiting pain, and has extremely important clinical significance for pain diseases.

The present application provides a kind of as sodium channel blocker and cyclophane compound and its use, it has inhibitory activity to sodium ion channel Nav1.8, can be used as the drug for treating a wide range of pain.

The invention belongs to the technical field of biological medicines, and relates to a mutants of mu-conotoxin KIIIA rich in positive charges and application of the mutants. The mutant is obtained by carrying out site-directed mutagenesis on C1A, K7R and C15R on a natural mu-conotoxin KIIIA sequence; the amino acid sequence of the mutant is shown as SEQ ID NO. 1 in a sequence table. According to the invention, a series of mutants which are simple and convenient to synthesize and have a remarkable inhibition effect on a NaV1.4 channel are obtained by performing systematic structural optimization on a parent peptide KIIIA containing three pairs of disulfide bonds and adopting a strategy of combining disulfide bond deletion and amino acid site-directed mutagenesis. Furthermore, non-natural amino acid Pen is introduced into the mutant with the optimal activity, so that the stability of the mutant in vivo is remarkably enhanced, and the action time is prolonged.

The invention discloses application of isotoosendanin in preparation of a medicine for relieving neuropathic pain and application of TRPV1 and Nav1.7 as medicine targets of the isotoosendanin, and relates to the technical field of biological medicine. The medicine prepared from the isotoosendanin can inhibit the expression of dorsal root ganglion (DRG) neurons TRPV1 and Nav1.7 protein; the medicine prepared from the isotoosendanin can inhibit the reduction of mechanical pain threshold and crymodynia threshold; the neuropathic pain comprises pain after selective injury of sciatic nerve branches; the TRPV1 and Nav1.7 are used as drug targets to be applied to preparation of the neuropathic pain relieving drug taking the isotoosendanin as an effective component. The isotoosendanin plays a role in relieving neuropathic pain, and the isotoosendanin can be used for inhibiting the expression of TRPV1 and Nav1.7; the isotoosendanin can be used for treating neuropathic pain by inhibiting expression of TRPV1 and Nav1.7 channel proteins, and a new thought is provided for preparing the neuropathic pain medicine.

The present invention relates to autoantibodies targeting the human NaV1.5 sodium channel and related isoforms as biomarkers for risk prediction of cardiac arrhythmias and sudden cardiac death in cancer patients, related methods and diagnostic kit for their detection.

The disclosure relates to the field of chronic pain and the treatment thereof. The disclosure involves antisense oligonucleotides and the use thereof in pre-mRNA and mRNA modulation, in one aspect related to RNA editing using endogenous ADAR enzymes, in targeting an adenosine in a (pre-) mRNA for human Nav1.7, preferably to change from a lysine residue to an arginine residue in the protein at position 1406 (K1406R), thereby impairing the ability of the Nav1.7 protein to act as a sodium ion channel. In another aspect the disclosure relates to exon skipping wherein antisense oligonucleotides are used to induce skipping of exon 23 in the generation of human SCN9A mRNA thereby generating a shortened Nav1.7 protein with an impaired ability to act as a sodium ion channel. The disclosure relates to methods and means to alter the Nav1.7 protein in cells of the peripheral nervous system, preferably large nociceptor cells (type Aα / Aβ), to provide a treatment of chronic pain.

The present disclosure relates to sulfonamide compounds, their use for modulating the sodium channel Nav1.5 and methods of treating or preventing diseases, disorders or conditions using the same.

Provided in the present invention are a substituted benzimidazole derivative, a preparation method therefor, and use thereof. The substituted benzimidazole derivative is represented by formula (I). The compound has a good Nav1.8 inhibitory effect and can be used for preventing and / or treating diseases associated with abnormal Nav1.8 channel activity, such as pain.

The present invention discloses a kind of polysubstituted pyrrolidine derivative compounds represented by the formula (I), stereoisomers, tautomers, deutero-derivatives or pharmaceutically acceptable salts thereof, as well as preparation methods and uses of the compounds and pharmaceutical compositions comprising the compounds, stereoisomers, tautomers, deutero-derivatives or pharmaceutically acceptable salts thereof, wherein the compounds can be used as sodium channel subtype Nav1.8 inhibitors, and their pharmaceutical use in the treatment and prevention of pain-related disorders.

The invention provides a polypeptide and application thereof. The amino acid sequence of the polypeptide is shown as SEQ ID NO: 1 or SE ID NO: 2. The 12th amino acid in the amino acid sequence of the polypeptide is alanine or glutamic acid; the nineteenth amino acid in the amino acid sequence of the polypeptide is methionine or leucine; the 28th amino acid in the amino acid sequence of the polypeptide is lysine or isoleucine; the 29th amino acid in the amino acid sequence of the polypeptide is selected from one of isoleucine, leucine and tryptophan. The polypeptide provided by the invention has a good analgesic function, can selectively inhibit activation of a Nav1.7 channel so as to inhibit pain, and has extremely important clinical significance on pain diseases.

The application provides a novel heterocyclic compound, a preparation method and a pharmaceutical use, and provides a new direction for development of a Nav1.8 inhibitor drug. The compound has good Nav1.8 inhibitory activity, good drug metabolism, and good drug properties. As a Nav1.8 inhibitor, the compound can be used for preventing and / or treating diseases related to abnormal expression of Nav1.8 channel activity, and has important clinical application value.

Disclosed are a five-membered heterocyclic compound, a pharmaceutical composition, and use thereof. Specifically provided is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The compound of the present invention has one or more of the following effect advantages: (1) a good blocking effect (or inhibitory effect) on the activity of the Nav1.8 channel; (2) a good pharmacokinetic profile; and (3) the potential to be used for treating Nav1.8-related diseases, such as pain.