20 results about "Histone Demethylases" 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.

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 belongs to the technical field of biological medicines, and particularly discloses application of inhibiting histone demethylase KDM4D in prevention and treatment of periodontitis. By constructing a mouse periodontitis and periodontitis animal model accompanied by systemic diseases, the influence of KDM4D intervention on periodontitis and periodontitis accompanied by systemic diseases is studied, and experimental results show that inhibition of KDM4D can down-regulate the expression level of osteoclast related genes, inhibit osteoclast differentiation, relieve alveolar bone resorption and bone loss, inhibit osteoclast differentiation and inhibit osteoclast differentiation. The traditional Chinese medicine composition has an obvious curative effect on periodontitis and periodontitis accompanied by systemic diseases, and a new prevention and treatment strategy is provided for periodontitis and periodontitis accompanied by systemic diseases.

This invention discloses a culture medium additive for improving embryonic developmental potential and its application, belonging to the field of in vitro embryo culture technology. This invention is the first to discover that CPI-455, a KDM5 histone demethylase inhibitor, can significantly improve the blastocyst rate, developmental speed, and embryo quality of preimplantation embryos by increasing H3K4me3 levels within a certain concentration range. Simultaneously, the addition of CPI-455 and NMN can substantially increase the rate of high-quality / high-quality blastocysts and embryo quality in in vitro embryo culture. The embryonic developmental potential additive provided by this invention is of great significance for improving in vitro embryo culture efficiency and embryo quality, accelerating the process of breeding superior embryos, and assisting in research on embryo-related mechanisms.

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 invention belongs to the technical field of biological medicines, and relates to application of histone demethylase KDM4A as a target spot, in particular to application of the histone demethylase KDM4A as the target spot in preparation of medicines for treating myocardial fibrosis and heart failure. The KDM4A is determined to be capable of mediating myocardial fibroblast aging so as to promote fibrosis of myocardial tissues and lead to heart failure. The invention provides a method for screening the medicine for treating myocardial fibrosis and heart failure by taking KDM4A as a target spot for the first time, and provides the medicine for treating myocardial fibrosis and heart failure, namely the medicine for regulating and controlling cardiac muscle fiber cell senescence to inhibit myocardial fibrosis.

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)pyridine-4-carboxylic acid, L-lysine salt, as histone demethylase inhibitors. Also provided herein are pharmaceutical compositions comprising such crystalline forms.

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.

This disclosure provides methods of preventing or treating cancer in an individual, comprising administering a therapeutic amount of an histone demethylase (LSD1) inhibitor and a therapeutic amount of a glycogen synthase kinase-3 (GSK-3) inhibitor to the individual, and compositions and kits usefule in performing such methods. Also provided are methods of determining the suitability of a cancer patient for treatment with a combination of a histone demethylase (LSD1) inhibitor and a glycogen synthase kinase-3 (GSK-3) inhibitor, and methods of monitoring the efficacy of such treatment.

Provided herein are methods for preparing 3-({[(4R)-7-{methyl[4-(propan-2-yl)phenyl]amino}-3,4-dihydro-2H-1-benzopyran-4-yl]methyl}amino)pyridine-4-carboxylic acid and novel intermediate compounds for use in preparing histone demethylase inhibitors.

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.

Provided herein are compounds for inhibiting Wnt signaling and methods of treating cancer. The compounds include any compound having a structure according to Formula II. The method includes administering one or more compounds according to Formula I and / or Formula II to a subject in need thereof.

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