50 results about "KEAP1" patented technology

The invention discloses tetrapeptide KA4 with an anti-fatigue function as well as a preparation method and application of the tetrapeptide KA4, and belongs to the technical field of biology. The tetrapeptide KA4 is screened from pacific salmon protamine enzymatic hydrolysate, the amino acid sequence is KYPA, and the tetrapeptide KA4 has strong binding capacity with KEAP1, AMPK and LDH, can significantly reduce the serum lactic acid content of a fatigue model mouse and significantly increase the load swimming time of the fatigue model mouse, has an anti-fatigue function, and can be applied to development of functional food for relieving fatigue.

The invention belongs to the technical field of protein, and relates to a peptide with liver protection activity and a preparation method and application thereof, and the amino acid sequence of the peptide is PFPRPQP. The active peptide can be used for activating a Keap1 / Nrf2 signal channel by reducing the liver enzyme level and inhibiting CYP2E1 expression so as to play a role in protecting HepG2 damaged cells. The invention also provides a preparation method and application of the liver-protecting active peptide.

The invention belongs to the technical field of food biology, and particularly relates to a sea cucumber-derived antioxidant peptide as well as a preparation method and application thereof. The sea cucumber source antioxidant peptide is prepared and screened from apostichopus japonicus and comprises at least one of peptides with the amino acid sequence shown as SEQ ID NO.1-4, and the docking energy of the peptides and a protein receptor Keap1 is-8.6 kcal / mol,-9.4 kcal / mol,-9.1 kcal / mol and-8.8 kcal / mol respectively. The antioxidant peptide obtained by the invention can be applied to food, cosmetics or medicines, and has important significance on the development of novel antioxidant products.

The invention provides an enteromorpha protein source antioxidant peptide as well as a preparation method and application thereof. Edible green algae enteromorpha is used as a raw material, the Keap1-targeted antioxidant peptide is screened from enteromorpha protein through methods of virtual enzymolysis, molecular docking, molecular dynamics simulation and the like, and the enteromorpha protein source antioxidant peptide has stable Keap1 binding capacity and remarkable antioxidant activity, and can be used for preparing a Keap1-targeted antioxidant peptide. The method can be widely applied to research and development of functional foods, medicines, skin care products, health products and the like, and has important economic values and good application prospects.

The invention discloses a hexapeptide LR6 with anti-inflammatory activity and a preparation method and application thereof, and belongs to the technical field of small molecule peptides. The amino acid sequence of the hexapeptide LR6 is LDAVDR, and the hexapeptide LR6 can be prepared through a solid-phase synthesis method and an enzymolysis method. The hexapeptide LR6 is identified from spirulina platensis proteolysis liquid and has potential interaction with Keap1, an LPS-induced RAW264.7 cell test shows that TNF-alpha, IL-1beta and IL-10 can be remarkably inhibited by treatment of low-dose (200mM) and high-dose (400mM) hexapeptide LR6, the inhibition effect of the high-dose hexapeptide LR6 is superior to that of positive control dexamethasone, and the inhibition effect of the high-dose hexapeptide LR6 is superior to that of positive control dexamethasone. Compared with dexamethasone, the hexapeptide LR6 has a better anti-inflammatory effect and can be used for preparing anti-inflammatory drugs.

The invention discloses a manganese-based nano-enzyme composite material as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) preparing Mn3O4-PVP from Mn3O4 NPs and PVP10, and then loading the Mn3O4-PVP into a ZIF-8 structure in the process that Zn < 2 + > and 2-MI react to form ZIF-8, so as to obtain Mn3O4-coated ZIF-8 NPs; (2) covering the surface of the Mn3O4 ZIF-8 with HA through ion coordination, and synthesizing MZH; and (3) carrying out clathration on MZH through ES100, and synthesizing MZH coated ES100. By inhibiting a TLR4 / NF-kappa B pathway, activating an Nfr2 / Keap1 pathway and increasing expression of intestinal tight junction protein, mouse colitis induced by DSS is resisted, and symptoms of the mouse colitis are relieved.

This invention relates to the field of bioactive peptide preparation technology, and discloses a method for preparing and applying a bifunctional antioxidant and anti-inflammatory peptide based on porcine skin collagen. The bifunctional peptide has the amino acid sequence GPSGPPGEKGP. Through peptidomics and computer simulation screening, this invention identified five novel antioxidant peptides with good solubility, non-sensitizing properties, and non-toxicity. Using an AFB1-induced HuH7 cell oxidative damage model, in in vitro cell experiments, GP-11 was shown to significantly reduce ALT, AST activity, and ROS levels, enhance the activity of SOD, CAT, and GSH-Px antioxidant enzymes, and activate the Keap1-Nrf2 pathway. It also reduced the levels of inflammatory factors TNF-α and IL-6 by downregulating the classical cGAS-STING inflammatory pathway. GP-11 exhibits both significant antioxidant effects and the ability to reduce the levels of inflammatory factors, demonstrating a dual function of antioxidation and anti-inflammation.

Mutant Cas9 proteins are described that have one or more mutations in a Keap1 degron sequence of the Cas9 protein. The one or more mutations can increase the half-life of the mutant proteins. Nucleic acid sequences and constructs comprising a sequence that encode a mutant Cas9 protein, as well as methods of enhancing CRISPR efficiency by administering one or more guide RNAs (gRNAs) to a cell comprising the mutant Cas9 proteins are also disclosed herein.

The invention discloses a molecular docking screening method and application of hermetia illucens protein antioxidant peptides, and relates to the technical field of biologication.The method comprises the following steps that S1, hermetia illucens protein is prepared through enzymolysis, wherein hermetia illucens defatted protein powder serves as a raw material, enzymolysis is conducted through pepsin under the enzymolysis conditions that the pH is 2.0, the temperature is 40 DEG C, the enzyme adding amount is 3% of the protein mass, the enzymolysis time is 3 h, and enzymolysis liquid is obtained; after the reaction is finished, inactivating, centrifuging, collecting supernatant, and freeze-drying to obtain hermetia illucens protein hydrolysate; according to the molecular docking screening method and application of the hermetia illucens protein antioxidant peptide, the molecular docking technology is specifically applied to efficient screening of the hermetia illucens-sourced antioxidant peptide, KEAP1 is taken as a key target, high-activity candidate peptide is rapidly and accurately positioned from massive enzymolysis peptide fragments, and the screening efficiency of the hermetia illucens-sourced antioxidant peptide is improved. The defects that a traditional blind screening method is large in workload, long in period and high in cost are overcome, and the screening efficiency and the success rate are remarkably improved.

The invention discloses screening of transcriptome biomarkers responsive to tanshinone IIA and application of the transcriptome biomarkers in sepsis diagnosis and treatment kits. Tanshinone IIA (TSA) inhibits an SAMSN1 gene in a targeted manner by up-regulating expression of mmu-miR-1896, so that an NRF2 / KEAP1 antioxidant pathway is activated, and GSDMD-mediated pyroptosis is inhibited, thereby reducing multi-organ injury. 10-20 mg / kg of TSA can significantly improve the alveolar structure of the LPS model and reduce inflammatory factors. A kit which is developed on the basis of the mechanism and is used for detecting the expression levels of mmu-miR-1896, SAMSN1 and NRF2-Kea1-GSDMD can be used for evaluating the curative effect.

The present disclosure relates to methods of co-administering PROTAC (proteolysis targeting chimera) compounds that can promote ubiquitination and degradation of a target protein. The present disclosure also relates to antibody drug conjugates of PROTAC compounds Also disclosed herein are pharmaceutical compositions that can include a compound of Formula (V), the use and preparation thereof.

Provided herein is a method for treating or preventing a disease or disorder associated with a deregulated NRF2 / KEAP1 pathway, comprising administering a subject in need thereof a therapeutically effective amount of entacapone or nitecapone or a pharmaceutically acceptable salt thereof; and entacapone or nitecapone can reversibly bind to KEAP1, those compounds activated NRF2 in vitro and in vivo by reversibly modifying C151 on KEAP1, and both drugs can enhance the expression of growth differentiation factor 15 (GDF15) and NRF2 downstream antioxidant response elements (ARE) genes.

The invention discloses an application of a fluorinated modified peptide in preparation of a medicine for treating dry age-related macular degeneration, the fluorinated modified peptide FNBP can effectively pass through a retinal barrier and exert antioxidant and neuroprotective effects in RPE cells, and the dry age-related macular degeneration is treated by activating a Keap1 / Nrf2 pathway. The new application of the fluorinated modified peptide in dry AMD treatment is provided for the first time, and a new strategy is provided for medicine development of posterior ocular diseases.

The present invention aims to provide a medicament capable of treating and / or preventing diseases associated with oxidative stress by inhibiting the protein-protein interaction between Keap1 and Nrf2 and activating Nrf2. The present invention relates to a compound represented by the following formula (1):wherein each symbol is as described in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. In addition, the present invention also relates to a medicament containing the aforementioned compound, for the prophylaxis and / or treatment of diseases involving oxidative stress selected from the group consisting of chronic kidney disease, non-alcoholic steatohepatitis, chronic obstructive pulmonary disease, radiation skin disorder, radiation mucosal disorder, cardiac failure, pulmonary arterial hypertension, Parkinson's disease, Friedreich's ataxia, multiple sclerosis, age-related macular degeneration, retinitis pigmentosa and glaucoma.

The present invention aims to provide a medicament capable of treating and / or preventing diseases associated with oxidative stress by inhibiting the protein-protein interaction between Keap1 and Nrf2 and activating Nrf2. The present invention relates to a compound represented by the following formula (1):wherein each symbol is as described in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. In addition, the present invention also relates to a medicament containing the aforementioned compound, for the prophylaxis and / or treatment of diseases involving oxidative stress selected from the group consisting of chronic kidney disease, non-alcoholic steatohepatitis, chronic obstructive pulmonary disease, radiation skin disorder, radiation mucosal disorder, cardiac failure, pulmonary arterial hypertension, Parkinson's disease, Friedreich's ataxia, multiple sclerosis, age-related macular degeneration, retinitis pigmentosa and glaucoma.

The invention discloses application of EIF3H in treatment of liver cancer. Research finds that MASH and hepatic fibrosis can be relieved by down-regulating fatty acid de novo synthesis of EIF3H, and tumorigenesis in an HCC mouse model induced by DEN + HFHC and HDTI + HFHC is inhibited. In mechanism, EIF3H is combined with FASN, and KEAP1 mediated FASN ubiquitination is antagonized, so that the FASN protein is stabilized. Therefore, EIF3H is a FASN deubiquitinase which is not illuminated previously, and drives the MASLD-HCC process by promoting fatty acid metabolism reprogramming. The EIF3H-FASN axis can be used as a therapeutic target of liver cancer.

Disclosed in the present invention are a KEAP1 modulator represented by general formula (I), or a modulator that modulates NRF2 activity by means of modulating KEAP1 activity, a pharmaceutical composition thereof, a preparation method therefor, and the use thereof in the preparation of a drug for prevention and / or treatment of indications related to KEAP1 and NRF2, in particular the treatment of cancers.

The invention discloses a trachinotus ovatus sourced acetylcholin esterase inhibitory peptide as well as a preparation method and application thereof, and belongs to the technical field of bioactive peptides. The acetylcholin esterase inhibitory peptide is any one of polypeptides with amino acid sequences as shown in SEQ ID NO. 1 to SEQ ID NO. 4. According to the invention, trachinotus ovatus is taken as a raw material, heptapeptides DLTDYLM, QGPIGPR, hexapeptide APDPFR and pentapeptide WGDAG with acetylcholin esterase inhibitory activity, antioxidant activity and Ca < 2 + > binding activity are obtained through enzymolysis and immobilized calcium ion affinity chromatography separation, and the action mechanism of chelating with acetylcholin esterase and Keap1 is defined. The polypeptide from trachinotus ovatus can be applied to preparation of acetylcholin esterase inhibitors, antioxidants and calcium supplements, and has a good application prospect.

The invention relates to the technical field of biology, and discloses an antioxidant peptide derived from fermented meat and application of the antioxidant peptide, the antioxidant peptide comprises minced pork, auxiliary materials and a composite leavening agent composition composed of lactobacillus sake and staphylococcus xylosus, and fermentation and maturation are carried out by controlling the inoculum size and adopting a two-stage temperature control process. The core innovation of the method is as follows: firstly, performing comprehensive peptide sequence identification on small molecular weight components extracted from a fermentation product by adopting liquid chromatography-tandem mass spectrometry, and then accurately predicting and locking a target antioxidant peptide from a peptide library by utilizing virtual screening technologies such as molecular docking and the like. The antioxidant peptide prepared by the invention can be used for effectively relieving cell oxidative damage induced by ethanol by activating a Kelch sample ECH associated protein 1-Nrf2 (Keap1-Nrf2) signal channel. According to the method, directional fermentation and computational biology are combined, a new normal form is provided for efficiently discovering novel active peptides from natural products, and the research and development efficiency is effectively improved.

The invention relates to the technical field of lung adenocarcinoma cell lines, in particular to a mouse Trp53 / Keap1 mutant lung adenocarcinoma cell line (Mus musculus) as well as construction and application of the mouse Trp53 / Keap1 mutant lung adenocarcinoma cell line. The mouse Trp53 / Keap1 mutant lung adenocarcinoma cell line (Mus musculus) constructed by the invention is delivered to the China Center for Type Culture Collection on May 18, 2025, and the preservation number is CCTCC (China Center for Type Culture Collection) NO: C2025163. The cell line is derived from a lung adenocarcinoma model of a C57BL / 6 strain mouse, carries the most common Keap1 mutation in lung adenocarcinoma, is the first known lung adenocarcinoma mouse cell line only carrying Keap1 and Trp53 mutations in the world at present, has the in-vivo tumorigenesis ability of the C57BL / 6 mouse, and fills the blank of the mouse mutant cell line in the level.

The invention belongs to the technical field of antioxidant peptides, and particularly relates to a laver protein source antioxidant peptide tolerant to pepsin and trypsin as well as a preparation method and application of the laver protein source antioxidant peptide. According to the invention, edible seaweed is taken as a raw material, and a Keap1-targeted antioxidant peptide is screened from seaweed protein by integrating virtual enzyme digestion, molecular docking and other methods. A cell test verifies that the tripeptide can target Keap1 to activate an antioxidant system, enhance the activity of intracellular antioxidant enzyme and remove cell reactive oxygen species (ROS), and can tolerate in-vitro degradation of pepsin and trypsin, and the absorption rate in an intestinal tract model established by human colorectal adenocarcinoma cells (Caoco-2) is 1.64%. The polypeptide has the potential of being applied to oral anti-oxidation health care products and external anti-oxidation cosmetic components, and has high medicinal economic value.

The present invention discloses shell nacre-derived antioxidant peptides, and a preparation method and application thereof. The shell nacre antioxidant peptides FYFPKYGR and GYFPSYY provided by the present invention both have strong cellular antioxidant activity. In order to explore the mechanism of action, we conducted a visual analysis of the conjugates of the peptide and Keap1. The study found that it can generate hydrogen bonds and hydrophobic interactions with some binding sites in the Keap1-Kelch domain, proving that it can competitively bind to Keap1, thereby releasing Nrf2 and activating the Keap1-Nrf2-ARE pathway. In summary, shell nacre antioxidant peptides are expected to be used in the field of cosmetics, providing a theoretical basis for the high-value utilization of shell nacre.

The application discloses a kind of hexapeptide LE6 with anti-inflammatory activity and its preparation method and application, belong to small molecule peptide technical field.The amino acid sequence of the hexapeptide LE6 is LEPGFE, and can be prepared by solid-phase synthesis method and enzymatic hydrolysis method.This hexapeptide LE6 is identified from polysiphondryalis protease hydrolysate, has potential interaction with Keap1, and is found that low-dose (200mM) and high-dose (400mM) hexapeptide LR6 treatment can significantly reduce cell TNF-alpha, IL-1beta and IL-10 level in LPS-induced RAW264.7 cell test, wherein, the reducing effect of hexapeptide LR6 on TNF-alpha is superior to positive control dexamethasone, and hexapeptide LR6 can be used for preparing anti-inflammatory drug.

The invention provides application of AH2QDS in preparation of medicines for improving chronic obstructive pulmonary disease, which comprises the following steps: establishing an SD rat COPD model and a human bronchial epithelial cell (HBE) cell model, and intervening and observing lung functions, lung histopathology, oxidative stress indexes, inflammatory factor levels and apoptosis by using AH2QDS; molecular docking is used for predicting expression of Keap1-Nrf2 protein, and immunoblotting verification of related protein is carried out. Results show that the AH2QDS can relieve lung tissue injury, improve lung functions (PEF and MMEF) of COPD rats, improve expression of antioxidant enzymes such as SOD, CAT and GSH-PX, and reduce levels, ROS and apoptosis of cell inflammatory factors TNF-alpha, IL-6, IL-1beta and IL-33 through Keap1-Nrf2. The AH2QDS activates a Keap1-Nrf2 pathway to improve the oxidative damage resistance of an organism and reduce the level of inflammatory cytokines, so that the lung function is improved.

The present invention relates to methods of identifying a subject for treatment with or treating a subject with a tricyclic AKR1C3 dependent KARS inhibitor of formula (I), or a pharmaceutically acceptable salt thereof. The methods may comprise determining in a subject sample a level of at least one of the following biomarkers: AKR1C3, NFE2L2, KEAP1, or CUL3, wherein an elevated level of the biomarker identifies the subject as being in need of treatment; or detecting in a subject sample a somatic mutation in at least one of the following genes: NFE2L2, KEAP1, or CUL3, wherein detecting the somatic mutation identifies the subject as being in need of treatment.

The invention discloses a molecular glue degradation agent screening method integrating SPR (Surface Plasmon Resonance) screening and multi-omics analysis and application of the molecular glue degradation agent screening method in the field of medicine, and relates to the technical field of biological medicine and medicine screening. And identifying the molecular glue degradation agent and the target protein thereof. By utilizing the method, it is proved that the natural product triptolide serving as the molecular glue degradation agent of the E3 ligase VHL can specifically induce IMP3 ubiquitination degradation. In addition, as a molecular glue degradation agent of Keap1 ligase, the podophyllotoxin can specifically recruit and degrade DDX52 and LDHB (layered double hydroxides). The invention not only provides an efficient molecular glue degradation agent screening and identification platform, but also provides important reference for rational development of the molecular glue degradation agent.

The present invention is based in part on the identification of biomarkers, including NQO1, NRF2 and KEAP1, predictive of cancer cell responsiveness to treatment with ML 329 or a derivative thereof.

The invention discloses an application of rutin in reducing ribosome toxicity stress reaction to relieve oxidative stress of poultry livers. Rutin blocks JNK and p38 activation caused by ZAK alpha by down-regulating expression of ribosome toxicity stress reaction key protein ZAK alpha, so that an Nrf2 / Keap1 signal channel is activated, and the effects of anti-oxidation defense and lipid deposition inhibition on liver cells are achieved; according to the invention, rutin with proper concentration is screened out and added into chicken liver cells, and then oxidative damage induction is carried out on the cells, so that the rutin is verified to be capable of preventing oxidative stress generation of the liver cells; meanwhile, after the ZAKalpha is over-expressed in the cells added with the rutin, the protection effect of the rutin is weakened; according to the application of rutin in targeting ribosome stress toxic reaction, a new thought is provided for resisting oxidative stress, and the rutin has important research and development value on selection of development of anti-oxidative stress compounds.