146 results about "Inflammasome" patented technology

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.

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.

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.

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.

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 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 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.

Described herein are methods of treating a hematological malignancy, including minimal residual disease in hematological malignancies, and methods of preventing relapse of hematological malignancies, the methods comprising administering an inflammasome modulator. In some embodiments the method of treatment comprises administering a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein the variables are as defined herein.

The invention relates to the technical field of medicines, in particular to application of AV-412. The invention relates to an application of AV-412 in preparation of an NLRP3 inflammasome inhibitor. The invention discloses application of AV-412 in preparation of a medicine for treating infectious shock. The invention discloses application of AV-412 in preparation of a medicine for treating acute liver injury. The invention discloses application of AV-412 in preparation of a medicine for treating acute peritonitis. The invention provides a new choice for medicines for preventing or treating NLRP3 inflammasome related diseases, and also provides a new medicine with treatment potential for infectious shock, acute liver injury and acute peritonitis.

Compounds for use as inhibitors of the NLRP3 inflammasome pathway are provided, such compounds being as defined by the compounds of formula (I) and containing a group R 1 , R 2 , R 3 , R 4 , and R 5 is defined herein, and the compounds may be useful, for example, as pharmaceutical agents for use in the treatment of diseases or disorders associated with NLRP3 inflammasome activity. [Formula 1] TIFF2026504424000139.tif33128

The invention relates to the technical field of medicines, in particular to application of garcinia cambogia ketone C. The invention relates to an application of gamboge C in preparation of an NLRP3 inflammasome inhibitor. The invention relates to an application of garcinia cambogia ketone C in preparation of a medicine for treating infectious shock. The invention relates to an application of garcinia flavone C in preparation of a medicine for treating acute liver injury. The invention relates to an application of garcinia flavone C in preparation of a medicine for treating acute peritonitis. The invention provides a new choice for medicines for preventing or treating NLRP3 inflammasome related diseases, and also provides a new medicine with treatment potential for infectious shock, acute liver injury and acute peritonitis.

The present disclosure relates to compounds that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising the compounds; and methods of treating cancer and disorders associated with inflammation and inflammaging.

The invention belongs to the technical field of medicines, and relates to an NLRP3 inflammasome inhibitor and application thereof. Specifically, the invention relates to a compound represented by a general formula (I), or a deuterated compound thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and the definition of each group is as defined in the specification. Researches show that the compound represented by the general formula (I), or a deuterated compound thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof has high biological activity on NLRP3 inflammasomes, and has important clinical development value Y-W-R3 (I) for treating NLRP3 related diseases.

Described herein are NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors and pharmaceutical compositions comprising the inhibitors. The subject compounds and compositions are useful for the treatment of diseases or disorders associated with the NLRP3 inflammasome pathway.

This disclosure provides antisense oligonucleotide compounds and compositions (e.g., pharmaceutical compositions) that target NLRP3 and / or NLRP1 mRNA, as well as methods for treating diseases or conditions associated with the expression of NLRP3 and / or NLRP1 mRNA, or the activation of the NLRP3 and / or NLRP1 inflammasome. Exemplary conditions in which these compounds and compositions are used include, among others, neurodegenerative diseases and inflammatory diseases such as autoimmune diseases.

The present invention relates to pyridazin-3-yl phenol compounds of formula (I): wherein R1, R2, R3, R4 and R5 are defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of diseases and disorders mediated by NLRP3. (I)

Provision of novel NLRP3 inflammasome constituent proteins. [Solution] A protein that binds to NLRP3, selected from (a) to (c) below. (a) Protein consisting of the amino acid sequence shown in Sequence ID No. 2 (b) A protein that contains an amino acid sequence in which one or more amino acids are deleted, substituted, inserted, or added in the amino acid sequence shown in Sequence ID No. 2, and which binds to NLRP3. (c) A protein that has at least 90% sequence identity with the amino acid sequence shown in Sequence ID No. 2 and that binds to NLRP3.

1-methyl-2-carboxyl-3-acetanilide indole compounds and applications thereof. The compounds can block the interaction between NLRP3 and NEK7, effectively inhibit the activation and assembly of NLRP3 inflammasome, and have good prevention and treatment effect on NLRP3 inflammasome related inflammatory diseases such as Alzheimer's disease and Parkinson's disease. Thus, the compounds can be used for preparing drugs for treating and / or preventing NLRP3 inflammasome related inflammatory diseases, and provide a new choice for the development of NLRP3 inflammasome small molecule inhibitors.

The invention relates to an application of a cembrane diterpenoid compound in preparation of a medicine for preventing or treating inflammasome mediated inflammatory diseases, the cembrane diterpenoid compound is separated from Sinaria flexiobis soft coral or Sinaria manaarenis soft coral, and the cembrane diterpenoid compound is cembrane diterpene lactone (cembrane). The invention further relates to a preparation method of the cembrane diterpenoid compound, and the application of the cembrane diterpenoid compound to preparation of the medicine for preventing or treating the inflammasome mediated inflammatory diseases.

The present disclosure relates to highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate and biomedical uses thereof. In particular highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate, is provided for enhancing bodily function and treating various disease states. The methods described herein provide for production of a highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate via processes external to the human body and administering effective amounts of highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate to human subjects to achieve a range of therapeutic benefits, including but not limited to, one or more of: inhibiting inflammasome activation, reducing pro-inflammatory cytokines, improving insulin sensitivity, enhancing mitochondrial biogenesis, and promoting muscle protein synthesis. Additionally, highly purified (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate is administered in an amount and frequency conducive to one or more of: improving cognitive function, reducing oxidative stress, enhancing cardiovascular health, and supporting neuroprotection. Methods for manufacturing and purifying (R)-3'-hydroxybutyl (R)-3'-hydroxybutyrate compositions to ensure high specificity and efficacy in therapeutic applications are also provided.

Biomarkers that can support the diagnosis of inflammatory diseases and methods of their use. [Solution] A composition and method for detecting inflammasome components in a sample from a subject as a marker for inflammasome-related diseases or disorders such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammatory aging, or traumatic brain injury. Methods for using such inflammasome markers to determine prognosis, prescribe treatment, and monitor response to treatment in subjects with inflammasome-related diseases or disorders such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammatory aging, or traumatic brain injury are also described.

The application discloses application of lactosylceramide in regulating inflammation related to bronchiectasis Pseudomonas aeruginosa infection. The application discloses, for the first time, the role of LacCer in amplification of inflammation related to bronchiectasis infection, proposes a new infection control mechanism from the perspective of metabolic regulation, and indicates that LacCer participates in regulation of inflammation by regulating the NLRP3 inflammasome related pathway, thereby providing a direction for targeted intervention. On this basis, the application further proves, through in-vivo experiments, that inhibition of LacCer synthesis can intervene in inflammation and lung injury related to bronchiectasis infection, thereby providing a new potential treatment strategy for control of inflammation related to bronchiectasis infection.

The invention discloses a triazinone compound and medical application thereof.The compound shown in the formula I and pharmaceutically acceptable salt of the compound can serve as an NLRP3 inflammasome inhibitor and can be used for preparing drugs for preventing or treating NLRP3 inflammasome mediated diseases.

The application provides an engineered platelet membrane nanocarrier for regulating ischemic microenvironment and a preparation method thereof. The engineered platelet membrane nanocarrier is composed of a nanoparticle (DY) and a platelet membrane formed on the surface of the nanoparticle (DY), wherein the nanoparticle (DY) is self-assembled by long-chain molecules DSPE-PEG 2000 -Arg-TK-CY-09, TK represents a ROS-responsive material, a sulfur ketal bond, CY-09 represents an anti-inflammatory drug CY-09 for inhibiting the activation and assembly of NLRP3 inflammasome, Arg represents L-Arg for producing NO, and DSPE-PEG 2000 represents an amphiphilic polymer. The engineered platelet membrane nanocarrier (DY@PM) provided by the application has high stability and biological safety, can target a lesion site, and can synergistically regulate ischemic microenvironment through multiple targets, and has a wide application prospect in the biomedical field.

The invention discloses an anemoside B4 derivative as well as a preparation method and application thereof, a compound anemoside B4 (abbreviated as B4 or AB4) is taken as a raw material, and the derivative is prepared by respectively carrying out nucleophilic substitution, electrophilic addition, esterification reaction or amidation and other reactions on C-19 exocyclic double bonds or C-28 carboxyl. The compound is used as an active component to prepare medicines with anti-inflammatory and immunoregulation effects. The invention discloses the effect of the B4 derivative on treating inflammatory diseases such as inflammatory bowel disease, atopic dermatitis, eczema and psoriasis for the first time, and the drug effect of the B4 derivative is superior to that of B4 or clinically common drugs. In addition, the invention also discloses that most B4 derivatives do not show obvious cytotoxicity to macrophages for the first time, can reduce the P-I kappa Ba protein level in LPS and ATP induced macrophage NF-kappa B signaling pathways, inhibit the activation of NLRP3 signaling pathways and obviously reduce the Pro-IL-1beta level (p is less than 0.05), namely inhibit the activation of inflammasome pathways, and the effect is superior to that of B4; the results show that the B4 derivative disclosed by the invention has better anti-inflammatory activity.

The invention relates to a diterpenoid compound in callicarpa uniflora, a preparation method and application, the structure of the compound is shown as a formula (1), the compound belongs to the field of natural medicinal chemistry, and the invention aims to protect the application of the compound in preparation of an NLRP3 inflammasome inhibitor for treating inflammation. The invention has the following outstanding beneficial effects: 1, so far, there is no report on a pharmaceutical composition with the formula (1) as an effective component in the prior art, and there is no report on the compound and the pharmaceutical composition thereof in preparation of anti-inflammatory drugs for treatment of inflammation; and 2, the compound obtained by research in the invention inhibits the expression levels of Caspase-1 and IL-1beta in a dose-dependent manner, and inhibits shearing maturation of GSDMD at the same time, which shows that the compound has a significant inhibition effect on NLRP3 inflammasome-mediated inflammatory reaction. According to the invention, the medicinal value of the clerodane diterpenoid compound in the callicarpa uniflora is expanded.

The application discloses a chalcone derivative with a structure shown in formula (I) or a pharmaceutically acceptable salt or a stereoisomer thereof and application thereof as an active ingredient in preparation of an NLRP3 inflammasome inhibitor and / or a STATs pathway inhibitor. The compound can selectively inhibit the activation of the NLRP3 inflammasome and can inhibit the STATs pathway, thereby treating or improving diseases related to the NLRP3 inflammasome and / or the STATs pathway, such as acute peritonitis and colitis, and can be used in preparation of a therapeutic drug for diseases related to the NLRP3 inflammasome and / or the STATs pathway.