359 results about "Inflammasome" patented technology

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 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.

To provide an NLRP3 inhibitor that is effective in treating and preventing diseases, disorders, and conditions mediated by the formation and proliferation of the NLRP3 inflammasome.SOLUTION: A compound of the formula (I) is provided, where T is independently selected from the group: 1) CR3, and 2) N; provided that zero, one or two of T, U, V and W are N; U is independently selected from the group: 1) CR4, and 2) N; V is independently selected from the group: 1) CR5, and 2) N; W is independently selected from the group: 1) CR6, and 2) N; R1 is selected from -C3-12 cycloalkyl, -C3-12 cycloalkenyl, and -C2-12 heterocyclic alkyl, and R2 is selected from aryl and heteroaryl.SELECTED DRAWING: None

The present invention relates to a pharmaceutical composition for the prevention or treatment of degenerative brain diseases, comprising selexipag or a pharmaceutically acceptable salt thereof as an active ingredient. Selexipag inhibits the expression and production of pro-inflammatory or inflammatory cytokines in brain tissue, inhibits the activity of microglia or astrocytes, inhibits NLRP3 inflammasome activity and CDK6 expression, reduces amyloid plaques, increases the expression of the amyloid beta-degrading enzyme IDE, and inhibits the hyperphosphorylation of tau protein and the expression of tau kinase, and thus can be effectively used as a novel therapeutic agent for the prevention or treatment of degenerative brain diseases, cognitive disorders, learning disabilities, or memory disorders.

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 provides application of baicalin in preparation of a medicine for treating streptococcus agalactiae induced mastitis, and relates to the technical field of medicine. A mouse is selected as an animal model to research the intervention effect and mechanism of the baicalin on the streptococcus agalactiae induced mouse mastitis inflammatory response, and it is clear that the baicalin can play a role in protecting the mouse mammary gland by regulating and controlling an NLRP3 inflammatory small body pathway; a reference basis is provided for treating the cow mastitis caused by streptococcus agalactiae infection by applying the baicalin.

The present disclosure relates to compounds that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with inflammation and inflammaging, including hearing loss and other diseases associated with aging.

The invention belongs to the technical field of biological medicine, and particularly relates to application of zinc pyrithione in inhibition of NLRP3 inflammasome activation. The technical problem to be solved by the invention is to provide a new choice for treatment of NLRP3 inflammasome related diseases. The technical scheme of the invention is application of zinc pyrithione in preparation of an NLRP3 inflammasome inhibitor. The invention finds that the zinc pyrithione can inhibit the activation of NLRP3 inflammasomes, and shows a good inhibition effect in mouse and human cells; zinc pyrithione is expected to become a candidate drug for treating NLRP3 inflammasome related diseases.

The invention discloses an application of a conjugated ketene skeleton bromophenol compound in preparation of an anti-gout drug, the conjugated ketene skeleton bromophenol compound comprises BP-50 and BP-47, and experiments prove that the conjugated ketene skeleton bromophenol compound has remarkable inhibitory activity on xanthine oxidase, and can be used for preparing anti-gout drugs. The invention further studies the inhibition effect of the conjugated ketene skeleton bromophenol compound on MSU-induced inflammation taking NLRP3 inflammasome as a core, both BP-50 and BP-47 can inhibit secretion of MSU-induced characteristic inflammatory factors IL-1beta in a concentration-dependent manner, BP-50 down-regulates expression of NLRP3 inflammasome components by inhibiting an MAPK / NF-kappa B signal channel, and BP-47 can inhibit MSU-induced inflammation taking NLRP3 inflammasome components by inhibiting MAPK / NF-kappa B signal channel. The activation of the NLRP3 inflammasome is inhibited by reducing the ROS content, so that the activity of the NLRP3 inflammasome is reduced. It is proved that the conjugated ketene skeleton bromophenol compound can be used for preparing the anti-gout medicine, has a remarkable technical effect and has a wide market application prospect.

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 invention relates to a composition for preventing or treating virus infection diseases containing taurodeoxycholic acid or a pharmaceutically acceptable salt thereof as an active ingredient. Specifically, inflammatory cells and inflammatory cytokines were found to decrease in the lungs of an influenza virus-infected animal model to which taurodeoxycholic acid or a pharmaceutically acceptable salt thereof was administered as an inflammasome inhibitor, and thus the inflammasome inhibitor containing taurodeoxycholic acid or a pharmaceutically acceptable salt thereof can be used as an active ingredient in the composition for preventing or treating virus infection diseases.

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 invention belongs to the field of neurobiology and drug research and development, and discloses application of NR3A as a protein target in screening or preparing drugs for preventing and / or treating depression-like behaviors. According to the invention, the expression of NR3A in hippocampus is enhanced by stereotactic injection of adeno-associated virus containing Grin3a gene. A chronic constraint stress (CRS) is adopted to induce a depressive mouse, and a sucrose preference test (SPT), a forced swimming test (FST) and an open field test (OFT) are adopted for identification. The expression of proteins such as NR3A, calpain 2 (Calpain2), neuron nitric oxide synthase (nNOS), 3-nitrotyrosine (3-NT), an NLRP3 inflammation complex and the like is detected by WesternBlot; and performing DHE staining to detect reactive oxygen species (ROS). By enhancing hippocampus NR3A expression, depression-like behaviors induced by CRS can be improved, signal cascade activated by calcium is inhibited, ROS generation and 3-NT expression are reduced, and neuroinflammation driven by NLRP3 inflammasomes is inhibited. The NR3A participates in depression-like behaviors induced by CRS, and the mechanism of the NR3A is related to calcium homeostasis regulation, ROS generation and inflammatory response driven by NLRP3 inflammasomes.

The present invention provides compounds of Formula (I), wherein all of the variables are as defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of disease and disorders mediated by NLRP3.

The invention discloses an NLRP3 small-molecule inhibitor and an application thereof. The NLRP3 small-molecule inhibitor is asiaticoside or an asiaticoside analogue. The invention provides an application of asiaticoside or an asiaticoside analogue in preparation of a medicine for regulating an NLRP3 inflammasome pathway to relieve neuroinflammation, in particular to an application in preparation of a medicine for preventing Parkinson's disease.

The invention relates to an NLRP3 inhibitor, a pharmaceutical composition and application of the NLRP3 inhibitor. Specifically, the invention provides a compound as shown in a formula 1, a pharmaceutical composition and application of the compound and the pharmaceutical composition in preparation of drugs for preventing or treating diseases related to abnormal activation of NLRP3 inflammasome. # imgabs0 #

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 application of chamomile in preparation of a medicine for treating intestinal diseases, and belongs to the technical field of medicines. The embodiment of the invention verifies the application of the chamomile in the preparation of the medicine for treating the bowel disease, the bowel disease is an inflammatory bowel disease, and the chamomile is an NLRP3 inflammatory body inhibitor. The embodiment of the invention shows that the chamaectin can relieve the rise of related pathological indexes of the mouse inflammatory bowel disease, can obviously relieve the pathological change of a mouse model with the inflammatory bowel disease, and can be used for treating the inflammatory bowel disease. The embodiment of the invention proves that the chamomile has the effect of an NLRP3 inflammatory body inhibitor, and the chamomile is used for treating the inflammatory bowel disease by inhibiting the activity of an NLRP3 signal channel, so that the application of the chamomile in preparing the medicine for treating the bowel disease is proved.

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