18 results about "Histone demethylation" patented technology

The present invention generally relates to compounds as a dual kinase-demethylase inhibitor useful for the treatment of diseases mediated by a kinase and / or a histone demethylase, such as inflammation, cancer, viral and bacterial infections, neurological and immunological disorders. Pharmaceutical compositions and methods for treating those diseases are within the scope of this invention.

The invention discloses application of a JMJD6-targeted reagent in preparation of a medicine for promoting myocardial cell proliferation. The medicine can promote myocardial cell proliferation after myocardial infarction and reduce the myocardial fibrosis scar area caused by myocardial infarction. AAV9 myocardial specific overexpression virus and JMJD6 myocardial specific knockout mice are utilized, and the positive effect of JMJD6 in promotion of P1 cardiac apex resection of newborn mice and regeneration and repair of injured hearts after myocardial infarction of adult mice is disclosed for the first time; the specific mechanism is that JMJD6 depends on the activity of histone demethylase, enrichment of active modification H4R3me2a and H3R2me2s in a PDK4 promoter region is removed, transcriptional expression of the H4R3me2a and the H3R2me2s is inhibited, an impaired heart energy substrate utilization mode is stimulated to be increased and converted from fatty acid oxidation energy supply to glycolysis oxidation energy supply, and then adult myocardial cell proliferation is effectively promoted. The regeneration and repair capability of the heart after myocardial infarction is greatly improved, and a new effective target spot is provided for clinical treatment of myocardial injury.

This invention relates to the field of anti-aging drug technology, specifically to the application of small molecule compounds in the preparation of anti-aging drugs. These small molecule compounds competitively block the interaction between KDM6A and the vacuolar ATPase V0 domain subunit ATP6V0C by targeting a specific small molecule binding pocket of the histone demethylase KDM6A, thereby inhibiting the demethylation activity of KDM6A on lysine residue 36 of ATP6V0C. These small molecule compounds can effectively downregulate aging-related β-galactosidase activity, improve cell cycle arrest, and reverse the senescent phenotype of nerve cells induced by the environmental pollutant GenX, making them particularly suitable for combating premature aging of nerve cells induced by perfluorinated and polyfluoroalkyl compounds such as GenX. This technical solution can solve the technical problem of the lack of drugs with clearly defined components, a clear mechanism of action, stable efficacy, and the ability to specifically alleviate aging in existing technologies, and has ideal prospects for widespread application.

The invention provides a histone demethylase gene HOVUSG0811000 related to powdery mildew resistance and an application of the histone demethylase gene HOVUSG0811000 related to powdery mildew resistance. The nucleotide sequence of the HOVUSG0811000 is as shown in SEQ ID NO. 1 (sequence identifier number 1). It is found for the first time that HOVUSG0811000 improves the resistance of highland barley to powdery mildew by regulating phenol amine metabolism, and the HOVUSG0811000 has a good application prospect in construction of powdery mildew resistant plant varieties.

The invention relates to the technical field of anti-aging drugs, in particular to application of a small molecule compound in preparation of anti-aging drugs. The small molecule compound competitively blocks the interaction between the KDM6A and a vacuolar ATP enzyme V0 structural domain subunit ATP6V0C through a specific small molecule binding pocket of targeted histone demethylase KDM6A, and further inhibits the demethylation activity of the KDM6A on 36th lysine of the ATP6V0C. The small molecule compound can effectively down-regulate the activity of senescence-related beta-galactosidase, improve cell cycle arrest and reverse nerve cell senescence phenotypes induced by environmental pollutant GenX, and is especially suitable for resisting nerve cell premature senescence caused by perfluorinated and polyfluoroalkyl compounds such as GenX. According to the technical scheme, the technical problem that drugs which are definite in component, clear in action mechanism, stable in curative effect and capable of pointedly relieving senescence are lacked in the prior art can be solved, and ideal application and popularization prospects are achieved.

The invention relates to the technical field of plant genes, in particular to a histone demethylase gene OsJMJ708 for regulating and controlling rice salt stress toughness and application, and the histone demethylase gene OsJMJ708 comprises the following steps: obtaining an OsJMJ708 mutant; identifying an editing target spot of the OsJMJ708 gene; the OsJMJ708 is planted in a water planting mode; carrying out salt stress tolerance identification on the OsJMJ708 mutant; a homozygous silent mutant genetic material is obtained based on a gene editing technology by taking a rice histone methylation modified gene OsJMJ708 as a target gene. And salt stress treatment is carried out by using 180mM NaCl. The result shows that after salt stress treatment, the OsJMJ708 knockout mutant shows a salt-tolerant phenotype. It is proved that the OsJMJ708 gene plays a negative regulation role in the rice salt stress process, and excellent gene information is provided for rice salt-alkali tolerance oriented molecular design breeding.

The application relates to the field of biotechnology and plant molecular breeding, and discloses a tomato JMJC1 gene in improving the resistance of plants to plant parasitic nematodes. The JMJC1 nucleotide sequence of the gene is shown as SEQ ID NO. 1, and the amino acid sequence of the encoded protein is shown as SEQ ID NO. 2. Research proves that, JMJC1 the gene is strongly induced and expressed by root-knot nematodes, the encoded protein has histone demethylase activity, can specifically remove H3K9me3 and H3K27me3 inhibitory methylation modification, thereby removing the inhibition on downstream resistance-related genes, and activating the high expression of defense genes (such as PDF , PI2 and the like). Phenotype identification shows that overexpression of the JMJC1 gene in tomatoes can significantly reduce the number of root knots, and greatly enhance the defense response and resistance of plants to southern root-knot nematodes.

The invention discloses a tomato histone demethylase SlJMJ7 mutant and application thereof, TGC at the 385th site of a wild type SlJMJ7 gene is mutated into TCA and cysteine Cys at the 385th site is mutated into serine Ser through an overlapping extension three-wheel PCR (Polymerase Chain Reaction) method, the mutant SlJMJ7C385S gene is obtained, the nucleotide sequence of the SlJMJ7C385S gene is as shown in SEQ ID NO: 2, and the amino acid sequence of the SlJMJ7C385S gene is as shown in SEQ ID NO: 4; the inhibition function of SlJMJ7 is specifically relieved through single-point mutation, the pleiotropic risk caused by gene knockout is avoided, the mutant protein can restore the ethylene synthesis and carotenoid accumulation pathway inhibited by wild type SlJMJ7, the maturation process is accelerated, the protein subcellular localization and expression level are not affected by mutation, and the continuity of the regulation effect is ensured. Through site-specific mutagenesis of a C385 site of SlJMJ7, the inhibition effect of the protein on tomato fruit maturity is successfully relieved.

Provided herein are crystalline forms of 3-({[(4R)-7-{methyl [4-(propan-2-yl) phenyl] amino}-3, 4-dihydro-2H-1-benzopyran-4-yl] methyl} amino) pyridin-4-carboxylic acid L-lysine salt as inhibitors of histone demethylase. Also provided herein are pharmaceutical compositions comprising such crystalline forms.

The present disclosure provides a new series of 8-hydroxyquinoline derivatives / analogs that are potent KDM4 inhibitors with high activity and selectivity against KDM4 enzymes. Also disclosed are the pharmaceutical compositions comprising such 8-hydroxyquinoline-based potent KDM4 inhibitors, or a pharmaceutically acceptable salt thereof, and method of use thereof, for treating cancer and neoplastic diseases and the like.

The invention discloses synthesis and application of 4-amine-2, 7-disubstituted quinazoline derivatives, and the structural general formula of the 4-amine-2, 7-disubstituted quinazoline derivatives is I, the 4-amine-2, 7-disubstituted quinazoline derivative disclosed by the invention shows a certain histone demethylase inhibitory activity, and can be used for preparing a histone demethylase inhibitor. The compound can be used as a histone demethylase inhibitor and is used for preparing medicines for treating various diseases mediated by histone demethylase.

The invention discloses application of a related gene for postponing soybean flowering and / or increasing fat content. The invention provides any one of the following applications of a substance for inhibiting GmJMJ19 and / or GmJMJ20 gene expression, inhibiting GmJMJ19 and / or GmJMJ20 protein activity or reducing GmJMJ19 and / or GmJMJ20 protein content: 1) delaying plant flowering; 2) cultivating late flowering plants; 3) reducing the expression of the plant florigen gene; 4) increasing the fat content of the plant seeds; 5) cultivating plants with high-fat grains; and 6) improving expression of plant fat metabolism related pathway genes. The CRISPR / Cas9 knockout vector disclosed by the invention is transferred into soybeans and is used for knocking out histone demethylase genes GmJMJ19 and GmJMJ20 in the soybeans, so that a knockout strain is obtained, and a soybean plant with delayed flowering time and increased grain fat is obtained.

The invention discloses an application of a histone demethylase gene Osjmj719 and an encoding protein thereof in regulating and controlling the plant height of rice. An overexpression vector of the Osjmj719 gene and a CRISPR / Cas9 knockout vector are constructed, rice is transformed, an overexpression Osjmj719 plant and an Osjmj719 knockout mutant plant are obtained, and the result shows that the plant height of the Osjmj719 knockout mutant is moderately reduced, and the plant height of the overexpression Osjmj719 strain is increased. Therefore, the Osjmj719 gene can be used for regulating and controlling the plant height of the rice, and a candidate gene resource is provided for improving and cultivating new germplasm of the rice by utilizing a molecular means.

The present application belongs to the technical field of biological medicine, and particularly relates to application of a reagent or method for inhibiting expression of lysine-specific demethylase 6B in preparation of a drug for preventing and treating heart diseases caused by administration of anticancer drugs. The present application inhibits the activity of a downstream target gene p53 by inhibiting expression of histone demethylation transferase member lysine-specific demethylase 6B, and affects the expression of an apoptosis-related protein, thereby playing an important promoting role in a pathological process related to cell apoptosis. Based on this principle, the present application takes lysine-specific demethylase 6B as a target to prevent and treat heart diseases caused by administration of anticancer drugs, improves heart function, provides heart protection for tumor patients after administration of anticancer drugs, and also provides a new drug research and development approach and a drug action target for diagnosis and treatment of heart failure or myocardial injury of tumor patients after drug treatment, and has very important medicinal value.

The invention provides application of histone demethylase GmJD5L in regulation and control of flowering time and plant height of soybeans. The method comprises the following step of: inactivating the histone demethylase GmJD5La and GmJD5Lb of the soybean. The method can solve the problem of lack of methods for regulating and controlling the soybean flowering period and plant type in the prior art, and is suitable for the field of soybean breeding.

To provide compositions and methods for ex vivo production, expansion, enrichment, and / or maintenance of hematopoietic stem cells.SOLUTION: There is provided a method of producing an expanded population of hematopoietic stem cells ex vivo. The method comprises contacting a population of hematopoietic stem cells with an agent of (a) a histone demethylase inhibitor selected from a particular group; (b) a TGFβ receptor inhibitor selected from a particular group; and (c) a histone deacetylase inhibitor selected from a particular group. The agent is present in an amount sufficient to produce an expanded population of hematopoietic stem cells.SELECTED DRAWING: Figure 48

The present invention relates to a bioactive polypeptide synthesized on the basis of histone demethylase, and the use thereof in the neural differentiation process of mesenchymal stem cells. Disclosed in the present invention are possible protein-protein interaction binding sites of histone demethylase KDM2B and histone methylate EZH2, and disclosed are the roles of KDM2B and the bioactive polypeptide synthesized on the basis of the same in the neural differentiation process of mesenchymal stem cells and the tissue regeneration of injured spinal nerves. On this basis, it is concluded that KDM2B and the bioactive polypeptide synthesized on the basis of the same may play a role in promoting the neural differentiation of stem cells from apical papilla and the regeneration of injured spinal nerves.