33 results about "ASK1" patented technology

This invention is directed to methods for identifying apoptosis signal-regulated kinase 1 (“ASK1”) inhibitors useful for preventing and / or treating cardiovascular disease. This invention also relates to methods for preventing and / or treating cardiovascular disease in an animal by administering to the animal an ASK1 inhibitor.

The present invention provides a drug for at least one of prevention and treatment of cardiac failure capable of suppressing cardiac depression and the onset of cardiac failure in ventricular remodeling, and a method for screening the drug. The drug for at least one of prevention and treatment of cardiac failure of the present invention contains a compound that inhibits a functional expression of ASK1 protein in a cardiomyocyte as an active ingredient, and a method for screening a drug for at least one of prevention and treatment of cardiac failure of the present invention includes selecting a medicinal component for at least one of prevention and treatment of cardiac failure from a drug candidate compound by using inhibition of a functional expression of ASK1 protein as an indication. As shown in FIG. 1, if ASK1 protein is removed, for example, the ventricle dilation can be attenuated in ventricular remodeling after myocardial infarction, pressure loading, or the like, which makes it possible to prevent and treat cardiac failure.

The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) inhibiting compounds of the formulawherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

The invention relates to a salt of a benzoylaminopyridine derivative and application thereof in medicines, further relates to a pharmaceutical composition containing the salt or crystal form or a combination thereof, and application of the salt or the crystal form or the pharmaceutical composition in preparing the medicines for preventing, treating or relieving diseases regulated by ASK1 of patients.

The invention relates to a salt of a benzoylaminopyridine derivative and application thereof in medicines, further relates to a pharmaceutical composition containing the salt or crystal form or a combination thereof, and application of the salt or crystal form or the pharmaceutical composition in preparing the medicines for preventing, treating or relieving diseases regulated by ASK1 of patients.

The invention relates to a salt of a benzoylaminopyridine derivative and application thereof in medicines, further relates to a pharmaceutical composition containing the salt or crystal form or a combination thereof, and application of the salt or crystal form or the pharmaceutical composition in preparing the medicines for preventing, treating or relieving diseases regulated by ASK1 of patients.

The invention relates to a salt of a benzoylaminopyridine derivative and application thereof in medicines, further relates to a pharmaceutical composition containing the salt or crystal form or a combination thereof, and application of the salt or crystal form or the pharmaceutical composition in preparing the medicines for preventing, treating or relieving diseases regulated by ASK1 of patients.

Described herein are compounds, including pharmaceutically acceptable salts, solvates, metabolites, prodrugs thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat non-alcoholic steatohepatitis and other diseases characterized by dysfunctional tissue healing and fibrosis.

The invention discloses a peroxiredoxin 1 binding protein and application thereof, and the peroxiredoxin 1 binding protein comprises one or more of TXN (Trx), ASK1, TPM3, CFL1, GTPBP4, DIRAS2 and PPP2R1A. By immunoprecipitation assay, the peroxiredoxin 1 binding protein can be bonded to peroxiredoxin 1, and nicotine can promote the binding of the peroxiredoxin 1 and the peroxiredoxin 1 binding protein. In oral precancerous lesions such as leukoplakia cells, the expression of the peroxiredoxin 1 binding protein is significantly increased, and the nicotine can regulate the expression of the theperoxiredoxin 1 binding protein. The peroxiredoxin 1 binding protein can be used as a molecular marker for diagnosing or preventing the oral precancerous lesions such as oral leukoplakia, preparing aPrx1 protein conjugate, or binding, labeling, identifying, enriching, sorting or purifying Prx1 overexpresses cells.

The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) inhibiting compounds of the formula (I); wherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

The present invention provides a partial peptide comprising the functional domain of a protein comprising an amino acid sequence which is the same or substantially the same as an amino acid sequence represented by SEQ ID NO:2 or SEQ ID NO: 4; a screening method and a kit therefor for a substance which regulates ASK1 activation, or a prophylactic or therapeutic substance for diseases associated with apoptosis or inflammation, which comprises using the protein or the partial peptide or a cell which produces the same, and optionally ASK1 or a partial peptide thereof or a cell which produces the same; and an agent for regulating apoptosis or inflammatory cytokine production, or a prophylactic or therapeutic agent for diseases associated with apoptosis or inflammation, which comprises a substance for regulating an activity of a protein comprising an amino acid sequence which is the same or substantially the same as an amino acid sequence represented by SEQ ID NO:2 or SEQ ID NO: 4.

The invention relates to the technical field of gene engineering and biological enzyme with an aim to provides a preparation method and application of microbial-source antioxidant protease. The amino acid sequence of the protease is as indicated in SEQ ID NO.1. The invention further the preparation method of the protease and the application of the protease in preparing drugs or health food used for inhibiting body aging and cell apoptosis. The protease is the important protease for oxidoreduction balance adjustment and plays an important role in biological oxidative stress and damage repair process, thereby being potential in application value in the anti-aging field. Through combination and regulation of factors of ASK1, NF-k and the like, body ageing and cell apoptosis are inhibited, cells can be subjected to damage repair and proliferation, cell ageing and cell apoptosis can be postponed, and the protease is one of important targets in tumor and cancer treatment; the protease is soluble in physical characteristic, natural activity is retained, and wide application prospect is achieved.

The invention discloses an indole ASK1 small-molecule inhibitor and a preparation method and application thereof. The inhibitor comprises a compound as shown in a general formula (I) and a stereoisomer or pharmaceutically acceptable salt thereof. Experimental data prove that the inhibitor has a certain treatment effect on non-alcoholic steatohepatitis and ulcerative colitis, and has a good application prospect.

The present invention provides a partial peptide comprising the functional domain of a protein comprising an amino acid sequence which is the same or substantially the same as an amino acid sequence represented by SEQ ID NO:2 or SEQ ID NO: 4; a screening method and a kit therefor for a substance which regulates ASK1 activation, or a prophylactic or therapeutic substance for diseases associated with apoptosis or inflammation, which comprises using the protein or the partial peptide or a cell which produces the same, and optionally ASK1 or a partial peptide thereof or a cell which produces the same; and an agent for regulating apoptosis or inflammatory cytokine production, or a prophylactic or therapeutic agent for diseases associated with apoptosis or inflammation, which comprises a substance for regulating an activity of a protein comprising an amino acid sequence which is the same or substantially the same as an amino acid sequence represented by SEQ ID NO:2 or SEQ ID NO: 4.

A method of treating or preventing a thrombotic disease in a subject in need thereof comprises administering to the subject an effective amount of a pharmaceutical composition comprising an inhibitor of an apoptosis signal regulating kinase 1 (ASK1) protein. A method of identifying an inhibitor of an apoptosis signal regulating kinase 1 (ASK1) protein useful for treating or preventing a thrombotic disease, comprising (a) contacting a candidate agent with a test sample comprising the ASK1 protein, and (b) comparing the ASK1 protein activity in the test sample with the ASK1 protein activity in a control sample that has not been contacted with the candidate agent, whereby a decrease in the ASK1 protein activity in the test sample compared with the control sample indicates that the candidate agent is an ASK1 inhibitor.

The present invention relates to apoptosis signal-regulating kinase 1 (“ASK1”) . inhibiting compounds of the formulawherein the variables are as defined herein. The invention also relates to pharmaceutical compositions, kits and articles of manufacture comprising such compounds, to methods and intermediates useful for making the compounds, and to methods of using the compounds.

The invention discloses a protein phosphatase 5-based phosphatase recruitment chimera (PHORCs) compound as shown in a formula I defined in the description as well as a preparation method and medical application thereof. The compound disclosed by the invention can be used for dephosphorylating p-ASK1 in gastric cancer MKN45 cells to different degrees, and can be used for remarkably inhibiting the activity of the ASK1 in vitro and in vivo, so that cycle-associated proteins are selectively reduced, and the compound has a cell proliferation inhibiting effect. The cell proliferation inhibition effect of the compound DDO-3711 is obviously better than that of an ASK1 small-molecule inhibitor TCASK10 group and a combined administration group of the ASK1 small-molecule inhibitor TCASK10 and a PP5 small-molecule activator P5SA-1, and the compound can be used for preparing medicines for treating related diseases such as gastric cancer and colon cancer.

Provided are compounds of Formula (I): including compounds of Formulas (II), (III) and (IV), wherein X, R1, R2, R3 and n are as defined herein, and pharmaceutically acceptable salts thereof, and methods for their use and production. These compounds can be useful, e.g., in the treatment of disorders responsive to the inhibition of apoptosis signal-regulating kinase 1 (ASK1).

The invention discloses an ASK1 inhibitor, a derivative, a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown as a formula I. The ASK1 inhibitor derivative relates to an isomer, a diastereoisomer, an enantiomer, a tautomer, a solvate, a salt of the solvate, a pharmaceutically acceptable salt or a mixture of the isomer, the diastereoisomer, the enantiomer, the tautomer and the solvate of the compound. The ASK1 inhibitor and the derivative thereof have an efficient inhibition effect on ASK1 kinase, and can be used for preparing drugsfor ASK1 kinase related diseases, the prepared drugs can play a drug effect at a molecular level and a cellular level, the application is wide, and the synthesis method of the compound is simple, convenient and easy to operate.

The invention discloses an apoptosis signal regulating kinase inhibitor and an application thereof. The apoptosis signal regulating kinase inhibitor is a compound represented by general formula I, anda tautomer or a pharmaceutically acceptable salt thereof. The apoptosis signal regulating kinase inhibitor is a compound with a novel structure. Pharmacodynamic experiments prove that the compound has good inhibition capability on an ASK1 receptor, can be used for effectively inhibiting fibrosis in vitro and has low toxicity on normal cells. Therefore, the compound provided by the invention can be used for treating various fibrosis and related diseases.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of ASK1 gene expression and / or activity, and / or modulate a ASK1 gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against ASK1 gene expression.

The invention discloses an application of apoptosis signal-regulating kinase 1 (ASK1) in screening drugs for preventing, relieving and / or treating steatohepatitis by taking N-terminal dimerization of ASK1 as a target. The invention further discloses a method for screening drugs for preventing, relieving and / or treating steatohepatitis by taking N-terminal dimerization of ASK1 as the target. The invention firstly discloses that the N-terminal dimerization of ASK1 has important significance on the phosphorylation activation of ASK1 and the signal path of ASK1-JNK, has an important regulation role in fatty degeneration of liver cells, and can promote the fatty degeneration development of the liver. By taking N-terminal dimerization of ASK1 as the target and detecting whether candidate substances inhibit the N-terminal dimerization of ASK1, novel drugs for preventing, relieving and / or treating steatohepatitis can be screened.

The invention discloses an application of apoptosis signal-regulating kinase 1 (ASK1) in screening drugs for preventing, relieving and / or treating steatohepatitis by taking N-terminal dimerization of ASK1 as a target. The invention further discloses a method for screening drugs for preventing, relieving and / or treating steatohepatitis by taking N-terminal dimerization of ASK1 as the target. The invention firstly discloses that the N-terminal dimerization of ASK1 has important significance on the phosphorylation activation of ASK1 and the signal path of ASK1-JNK, has an important regulation role in fatty degeneration of liver cells, and can promote the fatty degeneration development of the liver. By taking N-terminal dimerization of ASK1 as the target and detecting whether candidate substances inhibit the N-terminal dimerization of ASK1, novel drugs for preventing, relieving and / or treating steatohepatitis can be screened.

Described herein are compounds, including pharmaceutically acceptable salts and solvates thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat non-alcoholic steatohepatitis and other diseases characterized by dysfunctional tissue healing and fibrosis.

The invention provides a pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation. The pharmaceutical composition comprises an apoptosis signal-regulating kinase 1 (ASK1) inhibitor and a thyroid hormone receptor beta subtype (TR beta) agonist. The research shows that the apoptosis signal regulating kinase 1 (ASK1) inhibitor, the thyroid hormone receptor beta subtype (TR beta) agonist or the combination of the ASK1 inhibitor and the TR beta agonist can relieve the symptoms of a mouse with non-alcoholic steatohepatitis (NASH) induced by high fat and carbon tetrachloride and improve NASH related indexes, and has potential benefits for NASH patients.

The present disclosure relates to a method of preventing and / or treating liver disease comprising administering an ASK1 inhibitor in combination with a FXR agonist to a patient in need thereof.

The invention relates to the field of drug activity prediction methods, in particular to a method for predicting ASK1 inhibitory activity based on a quantitative structure-activity relationship model. The method comprises the specific steps of collection of the ASK1 small-molecule inhibitor, processing and optimization of a data set, division of the data set, screening of descriptors, establishment of a multiple linear regression model and verification of the model. Through the method, a prediction result can be quickly obtained, the method can be applied to an alternative library with a large number of inhibitors for screening, the model is high in accuracy and stable, has generality and wide applicability, and can quickly find a proper small-molecule inhibitor. The experiment cost is saved, and unnecessary resource waste is avoided. And a powerful basis is provided for the development of new drugs.