50 results about "NAV1" patented technology

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 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).

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 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 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.

The invention discloses a mu-type conotoxin peptide, polynucleotide encoded by the mu-type conotoxin peptide and application of the mu-type conotoxin peptide. The amino acid sequence of the mu-type conotoxin peptide is shown as SEQ ID NO. 1. The invention provides a mu-type conotoxin peptide with higher biological activity than wild-type mu-type conotoxin, which can specifically block a Nav1.4 channel and reduce muscle contraction so as to be helpful for preventing and reducing wrinkles, and also can provide local anesthesia and reduce muscle activity, thereby playing an important role in the fields of beauty and medical treatment.

The invention discloses a medicine for preventing and treating salicylic acid-induced tinnitus, which is prepared by the following preparation steps: step 1, single intraperitoneal injection of salicylic acid (350 mg / kg) can stably induce a rat to have reversible tinnitus-like behaviors (the rat has the tinnitus-like behaviors after treatment for 2-8 hours and disappears after 24 hours), and in addition, the salicylic acid (350 mg / kg) is injected into the intraperitoneal injection of salicylic acid (350 mg / kg); the chronic tinnitus can be stably induced by intraperitoneal injection of salicylic acid (200 mg / kg, twice a day and every 12 hours) for seven consecutive days; 3, selecting 8-week-old C57BL / 6J male mice, quantitatively detecting indexes including auditory interstitial pre-pulse inhibition, pre-pulse inhibition and ABR after salicylic acid treatment, 2 hours after salicylic acid treatment (300 mg / kg) treatment, seven days after recovery (excluding the influence of salicylic acid and anesthetics) and 2 hours after salicylic acid treatment and NBI-921352 administration, so as to evaluate the modulation effect of drugs on tinnitus behaviors and auditory functions, and finally evaluating the tinnitus behavior and auditory function. The NBI-921352 is administered in an intragastric administration way, the dosage is 23 mg / kg, and the medicine takes Nav1.6 as a definite action target and has the characteristics of safety and effectiveness.

The invention provides a substituted benzimidazole derivative as well as a preparation method and application thereof. The substituted benzimidazole derivative is shown as a formula (I). The compound has a good Nav1.8 inhibition effect, and can be used for preventing and / or treating diseases, such as pain, related to Nav1.8 channel activity abnormity.

We describe an artificial expression construct for rescuing voltage-gated sodium channel function by intein-mediated reconstitution of voltage-gated sodium channel alpha subunit 1 (Nav1.1), a protein encoded by SCN1A. Rescued voltage-gated sodium channel function can be utilized to treat disorders such as epilepsy, and more specifically, Dravet syndrome.

The present disclosure relates to radiotracers that selectively bind to voltage-gated sodium channels (e.g., NaV1.7 or NaVl.8) and which are useful for detecting, imaging, and / or quantifying the NaVs, e.g., using positron-emission tomography (PET). The disclosure is also directed to processes for preparing the radiotracers, and to the use of the radiotracers for imaging a tissue or a subject, e.g., in vivo. The disclosure is further related to methods of pain management and improved identification and diagnosis allowing for rapidly identifying the location of or source of pain. The disclosure also relates to growth mediums, cell cultures, and kits.

The invention discloses an anti-wrinkle peptide Ssm6a-S21 as well as a preparation method and application thereof, and belongs to the technical field of biology. The amino acid sequence of the anti-wrinkle peptide Ssm6a-S21 is as shown in SEQ ID NO. 1. The anti-wrinkle peptide Ssm6a-S21 provided by the invention is a 21 amino acid peptide obtained by designing and truncating based on a key functional region of natural centipede poison peptide mu-SLPTX-Ssm6a, the inhibitory activity on a Nav1.7 channel is retained, the molecular weight is remarkably reduced, the synthesis difficulty and potential toxic and side effects are reduced, and the skin permeability is improved.

This invention discloses the application of the scorpion venom polypeptide BmK AS in the treatment of chronic epilepsy. BmK AS exerts potent anti-epileptic and neuroprotective effects through a confluence mechanism. In a lycine-induced mouse model, BmK AS significantly shortened seizure duration, reduced seizure frequency, prolonged seizure latency, and improved cognitive and mental outcomes. Electrophysiologically, BmK AS nonlinearly inhibited multiple VGSC subtypes, with a particularly significant effect on Nav1.6, reducing peak sodium current by 43% at a concentration of 5 nM. Furthermore, BmK AS alleviated hippocampal neuroinflammation by inhibiting the NLRP1 inflammasome pathway and related pyroptosis. This invention establishes BmK AS as a promising multi-mechanism therapeutic candidate, highlighting the value of a dual therapeutic strategy of Nav1.6 blockade and neuroinflammation suppression for epilepsy treatment.

The present invention relates to a therapeutic compound, a novel RNA interference (RNAi) agent, that reduces the expression of the voltage-gated sodium channel α subunit 10 (SCN10A) gene, which encodes Nav1.8 or a subunit of the Nav1.8 sodium channel. Such RNAi agents reduce the level of intact Nav1.8 sodium channels and are useful in the treatment of diseases in which the regulation of SCN10A expression and function is involved, such as chronic pain.

A novel sodium channel modulator compound and its uses are presented below. The sodium channel modulator has a completely new structure as shown in formula I, and shows excellent in vitro inhibitory effect against Nav1.8. This compound or its pharmacologically acceptable salt can be used to treat sodium channel-related diseases, including diseases such as pain, multiple sclerosis, Charcot-Marie-Tooth disease, incontinence, pathological cough, or arrhythmia.