109 results about "NAV1" patented technology

The invention relates to a furan ring-containing compound as well as a pharmaceutical composition and application thereof. Specifically disclosed is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound provided by the invention has one or more of the following advantages: (1) the structure is novel; (2) the compound has a good retarding effect (inhibiting effect) on the activity of a Nav1.8 channel; and (3) the compound has good selectivity to other subtypes of Nav and is high in safety. # imgabs0 #

The present invention relates to novel compounds that inhibit Nav1.8 sodium channels, methods of making, and methods of using thereof. The present disclosure is further directed to administering the disclosed compounds as therapeutic solutions for acute, chronic, and neuropathic pain to a subject in need thereof.

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).

Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 1-723.

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 invention discloses a mu-type conotoxin peptide mutant as well as a pharmaceutical composition and application thereof. The amino acid sequence of the mu-type conotoxin peptide mutant is as shown in SEQ ID NO. 1. Compared with a wild type mu-type conotoxin peptide, the mu-type conotoxin peptide [d-Arg2, Ser17]-dR-mu-CnIIIC disclosed by the invention has higher activity, the animal activity is improved by more than 20 times, and muscle contraction can be effectively reduced by specifically blocking a Nav1.4 channel. In addition, the compound can be used as a non-invasive anti-wrinkle treatment means to reduce or eliminate the formation of wrinkles on the human skin surface, and has a wide application prospect in the fields of medical treatment and beauty.

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 present invention is directed to novel compounds that inhibit Nav1.8 sodium channels, methods of making, and methods of using thereof. The present disclosure is further directed to administering the disclosed compounds as therapeutic solutions for chronic pain, primary pain, idiopathic pain, gastrointestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer-related pain, idiopathic pain, postoperative pain, visceral pain, multiple sclerosis, Summer-Marr-Tuff syndrome, incontinence, pathological cough, or arrhythmia to a subject in need thereof.

Provided is a novel sodium channel modulator, in particular a Nav1.8 channel modulator, said compound being a compound of formula I, formula II, or formula III, an isomer thereof, a racemate thereof, or a pharmaceutically acceptable salt or prodrug thereof, wherein formula I is as shown.

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 is a novel sodium channel modulator, in particular a Nav1.8 channel modulator, the compound having a formula I, a formula II, or a formula III, an isomer, a racemate, or a pharmaceutically acceptable salt or prodrug thereof, where the formula I is as shown in the specification. # imgabs0 #

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.

The present invention relates to a furan ring-containing compound, a pharmaceutical composition thereof, and a use thereof. Specifically disclosed is a compound as 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 novel structure; (2) a good blocking effect (inhibitory effect) on the activity of a Nav1.8 channel; and (3) good selectivity for other subtypes of Nav and high safety.

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 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 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.