13 results about "Nrf2 activators" patented technology

The invention relates to an application of 5-selenoflavone serving as an Nrf2 activator in preparation of an anti-osteoporosis medicine. The Nrf2 activating agent is a 5-seleno flavone compound 5c, namely, 7-fluoro-2-(3-methyl phenyl)-5-(3-methyl phenyl seleno)-flavone 5c. According to the invention, it is found for the first time that the 5-selenoflavone compound 5c can directly form a non-covalent bond with Keap1Kelch domain to inhibit Keap1-Nrf2 protein-protein interaction, and the 5-selenoflavone compound 5c is a novel micromolecular Nrf2 activator. The Nrf2 activator has obvious anti-osteoporosis activity, can directly form a non-covalent bond with Keap1Kelch domain to inhibit Keap1-Nrf2 protein-protein interaction, activate Nrf2, inhibit ROS and inhibit MAPK and NF-kappa B signal channels, further effectively inhibits osteoclast differentiation and bone resorption activity thereof and inhibits in-vivo bone loss, can be used for preparing anti-osteoporosis drugs, and has broad application prospects. The invention provides a novel anti-osteoporosis medicine for clinic, and has better clinical application value and wide application prospect.

We provide a technology that can activate NRF2. [Solution] An NRF2 activator comprising one or more chondroitin sulfate oligosaccharides selected from (a) to (c) below as an active ingredient: (a) a disaccharide having a chondroitin sulfate structure (a disaccharide of CS), (b) a trisaccharide having two N-acetyl-D-galactosamine residues and a chondroitin sulfate structure (a trisaccharide of CS having two GalNac residues), (c) a tetrasaccharide having a chondroitin sulfate structure (a tetrasaccharide of CS). According to the present invention, NRF2 can be activated. This is expected to promote homeostatic reactions in the body, such as antioxidant reactions, anti-inflammatory reactions, and detoxification reactions, and contribute to maintaining and improving health. It is also expected to contribute to the prevention and improvement of various unhealthy conditions and diseases caused by oxidative stress, inflammation, and toxic chemicals.

The invention relates to application of odd-carbon fatty acid as an Nrf2 activator, in particular to application of the odd-carbon fatty acid or a composition containing the odd-carbon fatty acid to preparation of a medicament for treating and / or preventing Nrf2 pathway mediated diseases or symptoms. The invention also relates to an application of odd-carbon fatty acids or a composition thereof in preparation of an Nrf2 agonist and an application of an Nrf2 pathway agonist in preparation of a composition for improving physical conditions of pregnant and / or post-parturition mammals and newborn mammals.

Provided are: a therapeutic drug for chronic kidney disease, which is capable of significantly improving the chronic kidney disease; and a screening method for a therapeutic drug for chronic kidney disease. This therapeutic drug for chronic kidney disease comprises an Nrf2 activator to be used in combination with a renin-angiotensin inhibitor. This therapeutic drug for chronic kidney disease comprises a renin-angiotensin inhibitor to be used in combination with an Nrf2 activator. This therapeutic drug for chronic kidney disease comprises a renin-angiotensin inhibitor and an Nrf2 activator.

The present invention provides: an Nrf2 activator; and a pharmaceutical composition for preventing or treating diseases related to activation of Nrf2, comprising the Nrf2 activator. Accordingly, it is possible to effectively prevent or treat oxidative stress- or mitochondrial dysfunction-related neurological diseases or oxidative stress-mediated skin diseases.

The application belongs to the technical field of medicine preparation, and particularly relates to an Nrf2 activator and application thereof in preparation of medicine. The Nrf2 activator comprises a compound I and a traditional Chinese medicine extract; a mass ratio of the compound I to the traditional Chinese medicine extract is 1-10:0.5-5; the traditional Chinese medicine extract is one or more of an astragalus extract, a radix ginseng extract, a radix salviae miltiorrhizae extract and a radix smilacae extract. The Nrf2 activator is prepared into medicine for preventing or treating diabetic nephropathy together with a pharmaceutically acceptable carrier or excipient. The Nrf2 activator can target and activate an Nrf2 signal pathway, significantly inhibit accumulation of collagen and oxidative stress, and prevent and treat diabetic nephropathy.

The application discloses a dihydropyrimidine[4,5-d]pyrimidine-2(H)-ketone Nrf2 activator and a preparation method and application thereof. The compound has the following structural general formula: experiments prove that the compound can effectively activate the Nrf2 signal pathway to produce an antioxidative stress effect, thereby protecting nerve cells, and can be used for preventing and / or treating neurodegenerative diseases.

The present invention relates hydroxypyridoxazepine compounds, methods of making them, pharmaceutical compositions containing them and their use as Nrf2 activators. In particular, the invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, or a tautomer thereof, or a hydrate thereof.

The present application relates to the pharmaceutical use of a class of (E)-3-arylheterocyclyl prop-2-enoic acid derivatives. Such compounds are a class of new Nrf2 activators, which effectively activate Nrf2 signaling pathway to produce the effects of resisting oxidative stress, resisting neuritis, and enhancing mitochondrial function and biogenesis, thereby protecting nerve cells, and same can be used to treat neurodegenerative diseases and stroke. In addition, such new Nrf2 activators can also be used to treat autoimmune diseases, diabetes, nephropathy, and other chronic diseases.

Provided is use of a compound represented by Formula I or a pharmaceutically acceptable salt thereof as an Nrf2 activator. In Formula I, m is independently selected from an integer from 0 to 4, and R1 and R2 are independently selected from hydrogen, hydroxyl, halogen, C1-3 alkyl, halogen-substituted C1-3 alkyl, or C1-3 alkoxy. The Nrf2 activator is used for preparing a medicament for the treatment and / or prevention of diseases mediated by the Keap1-Nrf2 / ARE signaling pathway and / or diseases mediated by oxidative stress.

Vitiligo is a complex auto-immune skin disease resulting in melanocytes loss and skin depigmentation. Following-up on their previous work identifying mitochondrial DNA (mtDNA) in skin biopsies from some vitiligo patients, the inventors demonstrate here that melanocytes from non-lesional skin present elevated numbers of mtDNA variants associated with mtDNA release and can be classified as function of their number of mtDNA variants in low-variant (LV) and high-variant (HV) load. Vitiligo HV melanocytes display increased ROS production, reduced antioxidant capacity, elevated mitochondrial function and mtDNA release as compared to Vitiligo LV and healthy melanocytes. Sensing of mtDNA by the cGAS-STING pathway results in pro-inflammatory cytokine and chemokines production promoting the recruitment of cytotoxic CD8+ T cells. This cascade of events can be blocked with NRF2 activators suggesting new therapeutic approaches for sub-population of vitiligo patients displaying HV mtDNA phenotype. The present invention relates to method for the treatment of vitiligo in a subject in need thereof comprising a step of administrating to the subject a therapeutically effective amount of Nuclear factor erythroid 2 -related factor 2 (NRF2) activator.

Cerebral small vessel disease (SVD) is a leading cause of stroke and a major contributor to cognitive decline and dementia in the population. Evidences indicate that blood brain barrier dysfunction may play a significant role in VD pathogenesis. Recently, an inverse association of TRIM47 expression in brain and vascular tissues with extensive-SVD severity was reported in a human genome wide association study combined with summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers. Now, the inventors demonstrate TRIM47 is a key regulator of actin cytoskeleton organization through KEAP1 / NRF2 signalling pathway and might be protective from oxidative stress in brain EC. In particular, the in vitro TRIM47 knockdown decreases directed EC migration and delays EC adhesion process with loss of actin cortical reorganization and focal adhesion contacts. Furthermore, RNA sequencing and BioID results indicate that TRIM47 knockdown in brain EC, represses the expression of genes associated with cytoskeleton and NRF2 antioxidant pathway through a potential interaction with KEAP1. Accordingly, the present invention relates to the use of Nrf2 activators for the treatment of SVD.