286 results about "Inflammasome" patented technology

The invention relates to polypeptide gold nanoparticles modified by trace cigarette extract CSE (0.1%-1%) and application of the polypeptide gold nanoparticles in preparation of drugs for treating chronic obstructive pulmonary diseases. The polypeptide-modified gold nanoparticle is a polypeptide-modified gold nanoparticle as shown in a sequence SEQ ID NO: 1. It is confirmed for the first time that polypeptide (CLPFFD, SEQ ID NO: 1) gold nanoparticles modified by trace CSE (0.1%-1%) can antagonize mtDNA synthesis and inhibit mitochondrial ROS generation so as to inhibit activation of macrophage NLRP3 inflammasome, induce depolarization of macrophage and target lung macrophage in vivo to achieve anti-inflammatory activity, and the polypeptide (CLPFFD, SEQ ID NO: 1) gold nanoparticles can be used for preparing anti-inflammatory drugs. The compound has an obvious treatment effect in a COPD acute exacerbation model and a stable phase model, so that the compound can be used for preparing medicines for treating COPD. The medicine has the advantages of being remarkable in curative effect, capable of acting on specific cells in a targeted mode, convenient to track in vivo and the like, and a new treatment means is provided for COPD.

The invention belongs to the field of active peptides, and particularly relates to application of selenium-rich polypeptide in inhibiting NLRP3 inflammasome-related inflammations and regulating cholesterol transport protection lipid metabolism abnormality, the selenium-rich polypeptide is prepared by chelating Adi-Apo fusion protein as shown in SEQ ID NO: 3 and sodium selenite (Na2SeO3); the selenium peptide chelate has the effects of remarkably reducing the concentration of TC / TG in serum, reducing the liver lipid deposition and inflammation level and reducing the atherosclerotic plaque area proportion through high oxidation resistance and high anti-inflammatory activity, and can be used for treating and / or preventing lipid metabolism disorder diseases such as metabolism-related fatty liver diseases and coronary atherosclerosis.

The invention relates to an application of alvitinib in preparation of an NLRP3 inflammasome inhibitor. The alvetinib is used for preparing a medicament for treating infectious shock, a medicament for treating acute liver injury and a medicament for treating peritonitis. A new choice is provided for prevention or treatment of NLRP3 inflammasome related diseases, the problem of treatment of EGFR mutation lung cancer patients combined with NLRP3 inflammasome related diseases (infectious shock / acute liver injury / acute peritonitis) is solved, tumor progression and inflammatory response are inhibited at the same time through the Aviitinib (third-generation EGFR-TKI), and the NLRP3 inflammasome related diseases are treated through the Aviitinib (third-generation EGFR-TKI). It is suggested that the medicine is preferentially selected by the patients, and the medicine with higher treatment potential is provided for treatment of infectious shock medicines, acute liver injury medicines and acute peritonitis.

The invention relates to a probiotic preparation for improving Parkinson's disease and an application of the probiotic preparation. The bacterial strains in the probiotic preparation comprise an Ackermania muciniphila Akk11 bacterial strain and a Bifidobacterium breve BBr60 bacterial strain. The invention further relates to a preparation method of the probiotic preparation for improving the Parkinson's disease and an application of the probiotic preparation for improving the Parkinson's disease, wherein the bacterial strains in the probiotic preparation comprise the Ackermania muciniphila Akk11 bacterial strain and the Bifidobacterium breve BBr60 bacterial strain. The invention develops a brand-new probiotic compounding mode and a brand-new probiotic intervention strategy for improving the Parkinson's disease, that is, the Akk11 strain and the BBr60 strain are compounded, and the two strains are found to have potential interaction and can be matched with each other, so that a synergistic effect is achieved on the aspect of improving the Parkinson's disease, and the effect of improving the Parkinson's disease is achieved. Specifically, the traditional Chinese medicine composition synergistically improves dyskinesia caused by Parkinson's disease, reduces expression of related inflammatory factors in nigra, promotes generation of anti-inflammatory factors to relieve neurological inflammation, inhibits activation of inflammasome NLPR3 in nigra, and further inhibits brain inflammation.

The present application belongs to the technical field of medicines, relates to an NLRP3 inflammasome inhibitor and the uses thereof, and particularly relates to a compound represented by general formula (A) or a pharmaceutically acceptable salt, a stereoisomer and a tautomer thereof. The inhibitor has biological activity on NLRP3 inflammasome, and has important clinical development value for treatment of NLRP3-related diseases.

Disclosed are a Pulsatilla saponin B4 derivative, a preparation method therefor, and a use thereof. A compound Pulsatilla saponin B4 (referred to as B4 or AB4) is used as a raw material, a nucleophilic substitution reaction, an electrophilic addition reaction, an esterification reaction, or an amidation reaction is separately performed on a C-19 exocyclic double bond or a C-28 carboxyl group to prepare a derivative, and the derivative is used as an active ingredient to prepare a drug having anti-inflammatory and immunomodulatory effects. In the present invention, it is disclosed for the first time that the B4 derivative has the effect of treating inflammatory diseases such as inflammatory bowel disease, atopic dermatitis, eczema, and psoriasis, and the effect is superior to that of B4 or a clinically common drug. In addition, it is also disclosed for the first time that most B4 derivatives do not show obvious cytotoxicity to macrophages, and can reduce the level of P-IκBa protein in LPS and ATP-induced macrophage NF-κB signaling pathways, inhibit the activation of NLRP3 signaling pathways and obviously reduce the level of Pro-IL-1β (p<0.05), i.e., inhibiting the activation of an inflammasome pathway, and the effect is superior to that of B4. These results show that the B4 derivative of the present invention has better anti-inflammatory activity.

Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein X, A, R1, R2, R3, R4, and n are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of the NLRP3 inflammasome are also provided.

The invention provides an application of gastrodin in preparation of a medicine for treating peripheral neuropathy. According to the application disclosed by the invention, gastrodin can inhibit neuroinflammation mediated by microglia by inhibiting activation of an NF-kB / NLRP3 inflammasome signal channel, so that release of inflammatory factors is reduced, and neuropathy induced by bortezomib is relieved.

The present application relates to an NEK7 inhibitor, a pharmaceutical composition and a use thereof. The compound has a structural formula of formula (I). The compound of the present disclosure has good NEK7 inhibitory activity, and can be used for treating or preventing inflammatory pathological disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, atopic dermatitis, ulcerative colitis, Crohn's disease, cancer, osteoarthritis, gout, etc.) regulated by the NLRP3 inflammasome.

The present invention relates to a compound of formula (I) wherein R1 is a hydrogen atom, halogen or -(C1-C2)alkyl, R2 is -halo(C1-C2)alkoxy, and R3 and R4 form together with N to which they are attached an optionally substituted 5-7 membered monocyclic heterocycloalkyl ring or an optionally substituted 8-11 membered bicyclic heterocycloalkyl ring. The present invention also relates to a medicament and a pharmaceutical composition comprising said compound of formula (I), as well as their therapeutic uses, in particular as inhibitor of NOD-like receptor protein 3 inflammasome for preventing and / or treating Parkinson's disease, frontotemporal Dementia, Multiple System Atrophy, Alzheimer's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis or brain injury.

The present invention relates to compounds useful as inhibitors of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway, methods for preparing said compounds, pharmaceutical compositions comprising said compounds, methods of using said compounds and medicaments containing them in the treatment of various diseases and disorders, and their use in diseases and disorders mediated by NLRP3.

This specification generally relates to compounds of formula (I), formula (II), and formula (VI), and pharmaceutically acceptable salts thereof. Such compounds are useful for inhibiting NLRP3 inflammasome activity and may be useful as therapeutic agents. This specification also relates to the use of such compounds for treating or preventing diseases and conditions involving the NLRP3 inflammasome. This specification further relates to compositions comprising such compounds. (Formula (I), Formula (II), Formula (VI)) [Formula 1] JPEG2026503239000288.jpg82128

The invention discloses an NLRP3 inhibitor as well as a preparation method and application thereof. Specifically, the invention relates to a compound shown as a formula (NLRP3i-3) or a pharmaceutically acceptable salt thereof, the formula (I) is COCCNc1nc2c (c (= O) n (C) c (= O) n2C) n1Cc1cc (OC) ccc1N, and the chemical name is 8-((4-amino-2-methoxybenzyl)-7, 9-dimethyl-7, 9-dihydro-8H-purine-6, 8-diketone. The invention also provides a preparation method of the compound, a pharmaceutical composition containing the compound, and application of the compound in preparation of drugs for preventing and / or treating NLRP3-mediated diseases. The disease is preferably myocardial ischemia reperfusion injury. Experimental results show that the compound provided by the invention has excellent NLRP3 inhibitory activity (IC50lt, 100nM), and has high selectivity to NLRP3 inflammasomes; good pharmacokinetic characteristics are achieved in a rat body, and the bioavailability is high; in myocardial ischemia reperfusion injury models of mice and rats, the composition can significantly reduce myocardial infarction area, reduce myocardial enzyme level, alleviate inflammatory response and improve heart function; preliminary toxicological evaluation shows that the safety is good. Therefore, the compound disclosed by the invention is expected to be developed into a novel medicine for treating NLRP3 related diseases such as myocardial ischemia-reperfusion injury.

The present invention belongs to the field of chemical medicine and provides a compound represented by Formula I or a pharmaceutically acceptable salt thereof. The present invention provides a class of compounds with a skeleton of thiophenopyrrolotriazinone, which can be used to prepare NLRP3 inflammasome inhibitors and provides a new option for preparing drugs for treating diseases caused by abnormal activation of NLRP3 inflammasome.

Disclosed herein are methods, compounds, and compositions for treating or preventing an inflammasome-mediated disease or condition, including an inflammasome-mediated pulmonary disease or condition.

To provide methods for detecting inflammasome proteins as biomarkers of neurological disorders.SOLUTION: The present invention provides compositions and methods for detecting components of the inflammasome in a sample from a subject as markers for brain injuries such as multiple sclerosis, stroke or traumatic brain injury. Methods of using such inflammasome markers to determine prognosis, direct treatment and monitor response to treatment for the subject with a brain injury such as multiple sclerosis, stroke, mild cognitive impairment or traumatic brain injury are also described. Presented herein are inflammasome components useful as biomarkers with high sensitivity and specificity for various neurological or psychiatric conditions and methods of their use.SELECTED DRAWING: None

The invention provides medical application of a licochalcone B derivative CTG12 in preparation of an NLRP3 inflammasome inhibitor, and belongs to the technical field of biological medicine. The invention provides application of a licochalcone B derivative CTG12 in preparation of an NLRP3 inflammasome inhibitor. The invention also discloses application of the compound in preparation of drugs for preventing or treating diseases related to abnormal activation of NLRP3 inflammasomes. The synthesized compound CTG12 has the remarkable activity of inhibiting caspase-1 generated by BMDM cells, the effect is improved by about eight times compared with licochalcone B, and the compound CTG12 has the broad-spectrum and specific inhibiting effect and can effectively inhibit activation of NLRP3 inflammasomes.

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrade and / or otherwise modulate (e.g., inhibit) NIMA Related Kinase 7 (NEK7). Said chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having one or more disorders or diseases associated with NLRP3 inflammasome activation. Said disorders or diseases include but are not limited to, autoinflammatory and autoimmune disorders (e.g., gout, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease), cardiovascular and metabolic disorders (eg. pericarditis, atherosclerosis, Type 2 diabetes, obesity, and metabolic syndrome), fibrotic disorders (e.g. interstitial lung disease, chronic kidney disease), hematology (eg, anemia of inflammation) and eye disorders (eg. macular degeneration). In embodiments, and while not wishing to be bound by theory, it is believed that the chemical entities described herein directly target (e.g., directly bind to) NEK7, thereby altering (e.g., attenuating) the inflammatory response modulated by the NLRP3 inflammasome. This disclosure also features compositions containing the same as well as methods of using and making the same.

To provide methods and kits for inhibiting inflammasome activation in cells of a subject or an inflammation-affected eye in the subject.SOLUTION: A composition, which comprises a nucleotide sequence encoding a membrane independent CD59 protein operably linked to a promoter for expression and secretion of the membrane independent CD59 protein in cells of a subject or an inflammation-affected eye in the subject or a soluble CD59 protein and inhibits inflammasome activation, is administered to the subject.SELECTED DRAWING: None

The invention discloses a guaiane type sesquiterpene lactone quasi-natural product as well as a preparation method and application of the guaiane type sesquiterpene lactone quasi-natural product. The quasi-natural product and the derivative thereof are prepared by taking (R)-Carvone as an initial raw material through a chemical synthesis method. Experiments show that the guaiane type sesquiterpene lactone compound prepared by the invention has the effect of inhibiting red blood cell hemolysis, can be used as a candidate drug molecule for preventing and / or treating NLRP3 inflammasome related diseases, and has the potential of being developed into related anti-inflammatory drugs.

Compounds useful as inhibitors of the NLRP3 inflammasome pathway are provided wherein such compounds are as defined by a compound of formula (I) and wherein the radicals R1, R2, R3, R4, L and A are defined in the description, and wherein the compounds are useful as medicaments, for example, for use in the treatment of diseases or conditions associated with NLRP3 inflammasome activity.

The invention belongs to the technical field of gene editing and disease model construction, and particularly relates to a construction method and application of a Wilson disease animal model. Aiming at a large fragment deletion mutation type which exists clinically in Wilson disease but lacks a corresponding animal model, a CRISPR / Cas9 gene editing technology is utilized, a pair of sgRNAs is specifically designed, an eighth exon region of a mouse Atp7b gene is precisely cut and deleted, and a WD mouse model with deletion mutation (c.2333340delGACGGTGG) of eight basic groups of the eighth exon of the Atp7b gene is successfully constructed. The method can be used for research on pathogenesis of WD, screening of novel diagnostic markers and evaluation of curative effect of therapeutic drugs, is particularly suitable for preclinical evaluation of gene therapy strategies and development of adjuvant therapeutic drugs of targeted NLRP3 inflammasomes, and has great scientific research value and clinical transformation prospect.

The present invention relates to novel compounds of formula (I): wherein each of ring A, R1, R2, X, Y and Z is as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention also relates to a preparation method of the compound, a pharmaceutical composition and a medicament containing the compound, and application of the compound and the pharmaceutical composition and the medicament in treatment of NLRP3 mediated diseases and symptoms.

The invention relates to an NEK7 inhibitor, a pharmaceutical composition and application of the NEK7 inhibitor. The NEK7 inhibitor has a structural formula as shown in a formula (I). The compound disclosed by the invention has good NEK7 inhibitory activity, and can be used for treating or preventing a plurality of inflammatory pathological diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, atopic dermatitis, ulcerative colitis, Crohn's disease, cancer, osteoarthritis, gout and the like) regulated by NLRP3 inflammasome.

The present disclosure relates to compounds that act as inhibitors of the NLRP3 inflammasome, pharmaceutical compositions containing the compounds, and methods for treating inflammation and inflammation-aging-related disorders, including neurosensory disorders and other diseases associated with aging.

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrade and / or otherwise modulate (e.g., inhibit) NIMA Related Kinase 7 (NEK7). Said chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having one or more disorders or diseases associated with NLRP3 inflammasome activation. Said disorders or diseases include but are not limited to, autoinflammatory and autoimmune disorders (e.g., gout, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease), cardiovascular and metabolic disorders (eg. pericarditis, atherosclerosis, Type 2 diabetes, obesity, and metabolic syndrome), fibrotic disorders (e.g. interstitial lung disease, chronic kidney disease), hematology (eg. anemia of inflammation) and eye disorders (eg. macular degeneration). In embodiments, and while not wishing to be bound by theory, it is believed that the chemical entities described herein directly target (e.g., directly bind to) NEK7, thereby altering (e.g., attenuating) the inflammatory response modulated by the NLRP3 inflammasome. This disclosure also features compositions containing the same as well as methods of using and making the same.

The invention provides an application of resibufogenin or a pharmaceutically acceptable salt thereof in preparation of a medicine for treating atherosclerosis. The NLRP3 inflammasome is a multi-protein complex and participates in regulation and control of innate immune response, and abnormal activation of the NLRP3 inflammasome is related to occurrence and development of various diseases including atherosclerosis and the like. The resibufogenin targeted NLRP3 inflammasome is found for the first time and can be used for treating atherosclerosis. The NLRP3 inflammasome is used as a key regulatory factor of inflammatory response in atherosclerosis, and the abnormal activation of the NLRP3 inflammasome aggravates the disease progress. The invention provides a more effective anti-inflammatory treatment strategy by targeting the NLRP3 inflammasome.

The present invention provides novel markers of the severity of a central nervous system injury, such as spinal cord injury or traumatic brain injury, in a patient. In particular, protein components of inflammasomes in the cerebrospinal fluid that can be used to assess the severity of central nervous system injury in a patient are disclosed. Methods of using such protein biomarkers to determine a prognosis, direct treatment and rehabilitation efforts, and monitor response to treatment for a patient with a central nervous system injury are also described.

The present disclosure relates to compounds of Formula (I):and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as inflammatory, autoinflammatory and autoimmune diseases and cancers.

The invention belongs to the technical field of novel application of nattokinase, and provides application of nattokinase in preparation of a medicine for preventing and / or treating Parkinson's disease. According to the invention, an MPTP / MPP + induced Parkinson's disease (PD) in-vivo and in-vitro model is established, and a neuroprotection mechanism of nattokinase is disclosed by adopting a systematic experiment method. Results show that the nattokinase can significantly improve dyskinesia and intestinal dysfunction of MPTP-induced PD mice; the damage of dopaminergic neurons of the middle brain is effectively relieved, and the density of tyrosine hydroxylase positive neurons is maintained; the expression of TLR4 and NLRP3 inflammasome pathways and related proinflammatory cytokines is inhibited, and the neuroinflammatory response is relieved; pINK1 / Parkin expression is up-regulated, mitochondrial autophagy is activated, and damaged neurons are cleared. Direct association between nattokinase and Parkinson's disease prevention and treatment is established for the first time, an innovative solution is provided for developing a novel anti-Parkinson's disease medicine with dual effects of motor function improvement and neuroprotection, and the application has important development value in the field of treatment of neurodegenerative diseases.