62 results about "KEAP1" patented technology

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.

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 relates to the technical field of biological agents, in particular to abalone-derived polypeptide with antioxidant activity and a preparation method thereof. According to the invention, Haliotis discus hannai Ino is taken as a research object, a small peptide library is established by using a virtual enzymolysis technology from an important anti-oxidation pathway of cells, namely a Keap1-Nrf2 pathway, an abalone-derived anti-oxidation peptide DEDEDEDK with relatively strong binding capacity with Keap1 is screened out by using a molecular docking technology, and then, the anti-oxidation activity of the abalone-derived anti-oxidation peptide DEDEDEDK is verified by using a cell oxidative damage model, so that the abalone-derived anti-oxidation peptide DEDEDEDK can be used for preparing the anti-oxidation peptide DEDEDEDK with relatively strong binding capacity with Keap1. And a theoretical basis is provided for research and application of the antioxidant 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 relates to the technical field of bioengineering, and discloses a marker for predicting liver cancer treatment sensitivity and application thereof.The marker for predicting liver cancer treatment sensitivity comprises HECTD2, the nucleotide sequence of the HECTD2 is shown as SEQ ID NO: 1, oxidative stress of the HECTD2 is limited through KEAP1 / NRF2 so as to promote drug resistance of the revatinib, the marker comprises H3K181a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a, H3K182a The nucleotide sequence of the H3K18la is as shown in SEQ ID NO: 2, and the H3K18la induces up-regulation of HECTD2 in HCC cells, so that the drug resistance of the lenvatinib is promoted. According to the present invention, the HECTD2 is adopted as the E3 ubiquitin ligase, and the K48-connected multi-ubiquitin chain is added on the K551 residue of the KEAP1 so as to alleviate the oxidative stress stimulated by the treatment of the lenvatinib; the transcription of the HECTD2 is enhanced by the H3K18la; the expression level of the HECTD2 is an independent prediction index of prognosis of the HCC patient; a new visual angle is provided for understanding the drug resistance of the HCC to the lenvatinib, and a promising diagnosis and treatment strategy is possibly provided for clinical treatment of the HCC.

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.

The invention discloses a shell nacre layer source antioxidant peptide as well as a preparation method and application thereof. The shell nacre antioxidant peptides FYFPKYGR and GYFPSYY provided by the invention both have relatively strong cell antioxidant activity. In order to explore the action mechanism of the peptide, a conjugate of the peptide and Keap1 is subjected to visual analysis and research to find that the conjugate can generate hydrogen bonds and hydrophobic interaction with part of binding sites in a Keap1-Kelch structural domain, and the conjugate is proved to be capable of competitively binding with Keap1 so as to release Nrf2 and activate a Keap1-Nrf2-ARE pathway. In conclusion, the shell nacre antioxidant peptide is expected to be applied to the field of food or cosmetics, and a theoretical basis is provided for high-value utilization of the shell nacre.

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

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.

The present invention provides a goat casein protein hydrolysate, a preparation method and an application thereof. The goat casein protein hydrolysate provided by the present invention has an antioxidant effect, which is mainly achieved by regulating the types and contents of functional peptides therein. Among them, the functional peptides include peptide segments PWP, MPLW, PLW and LPW, which have biological activity, the potential to bind to and activate Kelch-like ECH-associated protein 1 (Keap1), and the ability to scavenge superoxide anions, and thus have an antioxidant effect.

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 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 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 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.