34 results about "Nrf2 activators" patented technology

The NF-E2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant defense and detoxification. To directly monitor stabilization of Nrf2 we fused its Neh2 domain, responsible for the interaction with its nucleocytoplasmic regulator, Keap1, to firefly luciferase (Neh2-luciferase). It is shown herein that Neh2 domain is sufficient for recognition, ubiquitination and proteasomal degradation of Neh2-luciferase fusion protein. The novel Neh2-luc reporter system allows direct monitoring of the adaptive response to redox stress and classification of drugs based on the time-course of reporter activation. The novel reporter was used to screen a library of compounds to identify activators of Nrf2. The most robust and yet non toxic Nrf2 activators found—nordihydroguaiaretic acid, fisetin, and gedunin-induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism.

The present invention is directed to a pharmaceutical composition comprising an Nrf2-inhibitor. Likewise, the present invention is directed to a pharmaceutical composition for use in the treatment of ASD in a patient, comprising: determining whether the patient suffers from ASD subtype 1 and administering a therapeutically effective amount of an Nrf2-inhibitor if the patients suffers from ASD subtype 1, wherein determining whether the patient suffers from ASD subtype 1 comprises administering the patient an Nrf2-activator and identifying the patient as suffering from ASD subtype 1 if he shows a negative response.

The invention discloses an NRF2 activator compound, drugs and new application of atractylenolide II, wherein the NRF2 activator compound is the atractylenolide II; the drugs are drugs for treating and preventing the diseases associated with NRF2 pathway regulation, and comprise the component atractylenolide II; the new application of the atractylenolide II is about the use of the atractylenolide II in preparing drugs or foods for treating or preventing the diseases associated with the NRF2 pathway regulation. Through a lot of exploration and research of the inventors, a plurality of compounds are tested and selected, and it is unexpectedly found that the atractylenolide II can be used as an effective NRF2 inducer. The experiments prove that the atractylenolide II can be used in the drugs for treating or preventing the diseases associated with the NRF2 pathway regulation. Particularly, the cell experiments and the animal experiments prove that the atractylenolide II has inhibitory effect on the growth of breast cancer cells.

The disclosure provides pharmaceutical compositions comprising Bach1 Inhibitors and Nrf2 Activators. The disclosure also provides methods of treating diseases such as psoriasis, multiple sclerosis, and COPD comprising administering a Bach1 Inhibitor and a Nrf2 Activator to a subject in need thereof.

The present invention comprises compositions having a.) at least one acetyltransferase EP300 inhibitor-substance, such as chemically pure spermidine or spermidine-rich wheat germ extract, and optionally b.) at least one nrf2 activator-substance, such as cocoa flavonoids. In use, a user typically adds said compositions to food during the day, and then consumes compositions with food. Typically, such additions are scheduled to occur regularly on consecutive days, for months and over years, such as edible bits of sprinkles-configuration added to meals and snacks, or other configurations as herein disclosed. Such compositions are typically consumed by user in divided doses each day, as disclosed herein.

In addition to its potent mechanism-dependent inhibition of estrogen biosynthesis, in accordance with the embodiments of the present invention, it has now been found that exemestane has novel chemoprotective properties which have hitherto not been explicitly recognized. The present invention provides methods for the use of compositions comprising exemestane for chemoprotection against a wide variety of non-mammary tumors (and possibly other chronic diseases) that are not estrogen-dependent, but have oxidative stress, inflammation and electrophile-damaging etiologies. The present invention also shows that exemestane shows powerful synergism with other classes of Nrf2-activators and phase 2 enzyme gene activators, including, for example sulforaphane (an isothiocyanate), shikonin (a naphthoquinone), zerumbone (a cyclic sesquiterpene) and resveratrol (a stilbene derivative), which increases the attractiveness of exemestane's novel uses.

The present invention is directed to a method for differentiating between ASD phenotype 1, phenotype 2 and other ASD patients, wherein the method comprises,: administering an Nrf2-activator to a subject, and identifying the subject as an ASD phenotype 1 patient if the subject shows a negative response, as a phenotype 2 patient if he shows a positive response and as another ASD patient if he does not show a positive nor a negative response, wherein the subject is a patient previously diagnosed with idiopathic ASD or a subject displaying clinical signs of ASD. Likewise, the present invention is directed to an Nrf2-activator for use in differentiating between autism spectrum disorder (ASD) phenotype 1 patients, phenotype 2 patients and other ASD patients, wherein the Nrf2-activator is administered to a subject, wherein a phenotype 1 patient is identified by a negative response, a phenotype 2 patient is identified by a positive response and other ASD patients are identified by the absence of a positive and a negative wherein the subject is a patient previously diagnosed with idiopathic ASD or a subject displaying clinical signs of ASD.

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 invention relates to compounds that are Nrf2 activators. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with Nrf2 activation.

Provided is FGF21 that is a metabolism-related biomarker reflecting the activation of Nrf2 in vivo. Also provided are a method for monitoring a response of a subject to which an Nrf2 activator is administered, said method comprising a step for measuring the FGF21 level, at a point during or after the administration of the Nrf2 activator, in a biosample that is derived from the subject, wherein an increase in the FGF21 level indicates a positive response to the administration of the Nrf2 activator, etc. According to the present invention, a metabolism-related biomarker that reflects the activation of Nrf2 in vivo is provided.

The present invention relates to bisaryl amide analogs, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to bisaryl heterocycles of Formula (I),

The invention relates to a pharmaceutical application of (E)-3-aromatic heterocyclic propyl-2-olefine acid derivatives. The compound is a novel Nrf2 activator, and has the effects of resisting oxidative stress, resisting neuritis and enhancing mitochondrial function and biogenesis by effectively activating an Nrf2 signal channel, so that nerve cells are protected, and the compound can be used for treating neurodegenerative diseases and cerebral apoplexy. In addition, such novel Nrf2 activators can also be used for the treatment of autoimmune diseases, diabetes and nephropathy as well as other chronic diseases.

The invention discloses a 1, 2, 4-oxadiazole Nrf2 activator-tacrine spliced product as well as a preparation method and application thereof. The structure of the compound is shown in the specification. According to the 1, 2, 4-oxadiazole Nrf2 activator-tacrine spliced product as well as the preparation method and application thereof of the invention, acetylcholin esterase inhibitory activity, Nrf2 activation activity, selective screening and Morris water maze experiments are used as carriers to evaluate the treatment of the Alzheimer's disease (especially moderate and severe Alzheimer's disease) by the compounds shown in the general formulas I, II and III, and the compounds have good in-vitro and in-vivo activity and extremely high selectivity, and can be used as precursor substances for further development of an anti-Alzheimer's disease effect by selectively inhibiting acetylcholin esterase and activating Nrf2.

The present invention relates to a compound which is (R)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl)propanoic acid (I), or a pharmaceutically acceptable salt thereof, in particular, the meglumine salt thereof, a pharmaceutical composition containing the compound and its use as an NRF2 activator.

The invention belongs to the technical field of preparation of medicines and health foods, and relates to an Nrf2 activator and application thereof in preparation of medicines / health food / dietary supplements. The Nrf2 activator comprises a compound I and a traditional Chinese medicine extract; the 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 codonopsis pilosula extract, a salvia miltiorrhiza extract and a Chinese yam extract. The Nrf2 activator and a pharmaceutically acceptable carrier or excipient are used for preparing medicines / health food / dietary supplements for preventing or treating diabetic nephropathy. The Nrf2 activator can activate an Nrf2 signal channel in a targeted mode, remarkably inhibit the accumulation and oxidative stress of collagen and prevent and treat diabetic nephropathy.

The present invention relates to a novel halo-(3-(phenylsulfonyl)prop-1-enyl)pyridine derivative or a pharmaceutically acceptable salt thereof; a preparation method thereof; and an Nrf2 activator and a pharmaceutical composition for preventing or treating diseases induced by a decrease in Nrf2 activity, both of which comprise the same as an active ingredient.

The present invention relates to compounds that are Nrf2 activators. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with Nrf2 activation.

The invention discloses an application of an Nrf2 activator to preparation of an anti-artificial joint wear particle induced osteolysis drug. Researches show that artificial joint wear particles can inhibit expression of a cell kernel factor E-2-related factor 2 (Nrf2), and reduce activity of an anti-oxidation reaction element (ARE) regulated and controlled by the downstream of the Nrf2, reduced capacity of controlling an oxidation-reduction reaction in a cell causes active oxygen (ROS) and a lipid peroxidation product malondialdehyde (MDA) in osteoblast to be increased, so that the ROS generation and degradation homeostasis is disordered, the activity of the osteoblast is inhibited, and the balance between osteoclast and the osteoblast is broken. After the Nrf2 activator Oltipraz is added, the content of the ROS in cells can be obviously reduced, and the generation of the lipid peroxidation product MDA is inhibited. In addition, a mouse skull dissolution model is established by implanting CoCrMo nano wear particles under the skin of a mouse skull, effective intervention is applied by intraperitoneal injection of Oltipraz, and in-vivo experiments further prove that the Oltipraz has a remarkable inhibition effect on osteolysis induced by the artificial joint wear particles.

The present invention relates to indane 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) or Formula (II), and pharmaceutically acceptable salts thereof:

The present invention relates to highly efficient Nrf2 activators-CO-releasing molecules of formula (I) and (II) capable of increasing HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in particular their use in the treatment of inflammatory or cardiovascular diseases, wherein CORM represents a carbonyl metal complex chosen from among: Mn(CO)5, formula (III), (IV), (V), (VI), (VII), (VIII) and (IX).

The present invention relates to the use of an NRF2 activator to treat respiratory diseases. In particular, the present invention relates to the treatment of respiratory diseases, in a mammal, in which related organ failure accompanied by accumulation of alveolar fluid, hypoxemia, cough, wheezing, dyspnea, hyperpnea and pulmonary inflammation has occurred.

The present invention relates to a novel halo-(3-(phenylsulfonyl)prop-1-enyl)pyridine derivative or a pharmaceutically acceptable salt thereof, a method for producing same, and an NRF2 activator and a pharmaceutical composition which comprise same as an active ingredient, the pharmaceutical composition being for preventing or treating diseases induced by a reduction in NRF2 activity.

The present invention relates to the field of biomedicine, in particular to a recombinant plasmid for screening Nrf2 activators and its construction method and application, wherein the recombinant plasmid comprises one or more than two antioxidant response elements connected in series, basic transcription elements, secreted Luciferase gene, secreted alkaline phosphatase gene. Compared with the prior art, the present invention uses secreted luciferase as a reporter gene, which has high detection sensitivity and does not need to lyse cells when detecting luciferase gene activity, thus realizing high-throughput screening and comparison of antioxidants, as well as long-term effects The detection of antioxidants provides an efficient, fast and simple method for screening antioxidants or detecting antioxidant activity, which can be applied to the screening of natural medicines and synthetic compounds with antioxidant effects.

In addition to its potent mechanism-dependent inhibition of estrogen biosynthesis, in accordance with the embodiments of the present invention, it has now been found that exemestane has novel chemoprotective properties which have hitherto not been explicitly recognized. The present invention provides methods for the use of compositions comprising exemestane for chemoprotection against a wide variety of non-mammary tumors (and possibly other chronic diseases) that are not estrogen-dependent, but have oxidative stress, inflammation and electrophile-damaging etiologies. The present invention also shows that exemestane shows powerful synergism with other classes of Nrf2-activators and phase 2 enzyme gene activators, including, for example sulforaphane (an isothiocyanate), shikonin (a naphthoquinone), zerumbone (a cyclic sesquiterpene) and resveratrol (a stilbene derivative), which increases the attractiveness of exemestane's novel uses.