35 results about "Histone methyltransferase" patented technology

The invention discloses a recombinant genetically engineered bacterium for producing a micafungin precursor FR901379 and an application of the recombinant genetically engineered bacterium. The recombinant genetically engineered bacterium for producing the micafungin precursor FR901379 is obtained by performing overexpression on an epigenetic modification factor in a phomopsis sheathing genome and performing screening to obtain the recombinant genetically engineered bacterium for producing the micafungin precursor FR901379. The epigenetic modification factor comprises a histone methyltransferase (Dot 1), a histone methyltransferase (Set2) or a histone deacetylase (Rpd3). The yield of FR901379 produced by the engineering strain is increased by 40% compared with that of an original strain. The method disclosed by the invention has the characteristics of simplicity and convenience in operation, high transformation efficiency and good genetic stability.

The present invention relates to pharmaceutical compositions comprising inhibitor(s) of human histone methyltransferase EZH2, and methods of cancer therapy using the EZH2 inhibitor(s).

The present disclosure provides compounds of Formula I that are inhibitors of the histone methyltransferase polycomb repressive complex 2 (PRC2) and its subunits, including embryonic ectoderm development (EED) proteins, and are therefore useful for treating diseases treatable by inhibiting dysregulation of PRC2 and EED, such as cancer. Pharmaceutical compositions containing such compounds and methods for preparing such compounds are also provided. In certain embodiments, the subject matter described herein is directed to compounds of Formula I, including all of the subformulas of Formula I, or pharmaceutically acceptable salts or solvates thereof. JPEG2026504602000095.jpg5157

The invention provides application of histone methyltransferase EZH2 as a therapeutic target of diabetic nephropathy podocyte senescence and injury, and relates to the technical field of biological medicine. It is found that the expression level of EZH2 in podocyte under the high glucose condition is remarkably increased, and conditions are provided for taking EZH2 as a biomarker for diagnosing or evaluating diabetic nephropathy podocyte damage and senescence. Subsequently, it is verified that podocyte damage of db / db mice can be remarkably improved, proteinuria of the db / db mice can be reduced, pathological damage of kidneys can be relieved, glomerular senescence of the db / db mice can be delayed, damage and senescence of podocytes under the high-glucose condition can be remarkably improved, the purpose of protecting the kidneys is achieved, the development of diabetic nephropathy is delayed, and the development of diabetic nephropathy is delayed. Therefore, the EZH2 can be used as a potential target for treating diabetic nephropathy.

Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

The present disclosure provides methods and pharmaceutical compositions for treating or slowing the progression of cancers that overexpress the histone methyltransferase WHSC1, e.g., t(4;14) multiple myeloma, by administrating to a subject in need thereof a therapeutically effective amount of an inhibitor of the histone methyltransferase, SETD2.

The present disclosure provides compounds of Formula I that are inhibitors of histone methyltransferase multi-comb inhibition complex 2 (PRC2), including embryonic ectoderm development (EED) protein, and its subunits, and are thus useful in the treatment of diseases that can be treated by inhibition of disorders of PRC2 and EED, such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Compositions are disclosed that include a combination of at least one histone deacetylase inhibitor with at least one DNA or histone methyltransferase inhibitor. The combination of the histone deacetylase inhibitor with the methyltransferase inhibitor synergistically induces antimicrobial host defense peptide gene expression.

The invention belongs to the field of biological medicines, and particularly discloses a novel application of a histone methyltransferase G9a inhibitor in preparation of a medicine for treating xerophthalmia. The invention discovers that the histone methyltransferase G9a inhibitor has an autophagy regulation effect for the first time, and by using the G9a inhibitor UNC0642, the rising inflammatory factors, active oxygen levels and apoptosis rate in the xerophthalmia can be reduced, and the symptoms of the xerophthalmia can be relieved in an animal model. The invention provides a potential molecular therapeutic target for effectively treating xerophthalmia, and has good practical application value.

This invention belongs to the field of pharmaceutical technology, specifically relating to novel substituted benzoylpyridinone compounds and their applications. These novel substituted benzoylpyridinone compounds have the general structural formulas shown in (Ⅰ), (Ⅱ), (Ⅲ), (Ⅳ), (Ⅴ), (Ⅵ), (Ⅶ), (Ⅷ), or (Ⅸ), and as antitumor drugs, they exhibit significant EZH2 histone methyltransferase inhibitory activity. This invention provides methods for preparing these compounds, as well as pharmaceutical compositions containing them and their uses. The novel substituted benzoylpyridinone compounds obtained by this invention possess more significant antitumor activity and safety, and are of great value, particularly as antitumor agents, in EZH2, PRC2, and EZH2 / PRC2-mediated diseases.

The present invention is inter alia concerned with an inhibitor selected from the group consisting of a selective KMT9-inhibitor, a selective METTL21A-inhibitor and a selective METTL21B-inhibitor for use in the treatment of cancer. KMT9, METTL21A and METTL21B are characterized herein for the first time as histone methyl transferases, and inhibitors of the same can be used for treating cancer.

The present invention belongs to the technical field of cellular anti-aging, and specifically relates to a small-molecule compound composition capable of reversing the senescence of an adult stem cell and restoring the regeneration activity thereof, and a method for reversing cellular senescence by means of using a chemical small-molecule composition and the use thereof. The composition capable of reversing cellular senescence comprises a WNT / β-catenin agonist, a TGF-β receptor inhibitor, an RAR agonist, a Smoothened receptor agonist, a multi-target inhibitor of the VEGFR and PDGFR families, a histone methyltransferase inhibitor, and a JAK1 / 2 inhibitor. The composition effectively solves the problem of the weak proliferation and regeneration potential of senescent adult stem cells, effectively reverses the senescence of the adult stem cells and maintains the intrinsic biological characteristics of the cells, and can thus improve and enhance the efficacy of clinical autologous cell transplantation therapy and cell derivative therapy.

Disclosed herein are compounds, compositions, and methods for inhibiting a histone methyltransferase. The compounds are verticillin derivatives that exhibit anti-proliferative activity against cancer cells. The compounds, compositions, and methods can be used to treat a subject with cancer.

This invention relates to methods for treating cancer, providing methods for treating solid tumors, B-cell lymphomas, or cancers with abnormal H3-K27 methylation, the method comprising orally administering a dosage form of EPZ-6438 in a therapeutically effective amount to a subject in need. This invention also relates to pharmaceutical compositions comprising one or more inhibitors of the human histone methyltransferase EZH2, and methods for treating cancer using such one or more EZH2 inhibitors.

The present invention is inter alia concerned with an inhibitor selected from the group consisting of a selective KMT9-inhibitor, a selective METTL21A-inhibitor and a selective METTL21B-inhibitor for use in the treatment of cancer. KMT9, METTL21A and METTL21B are characterized herein for the first time as histone methyl transferases, and inhibitors of the same can be used for treating cancer.

The present invention relates to novel therapeutic compositions and methods for treating cancer. In particular, the use of proteinaceous inhibitors, including novel bicyclic peptide inhibitors, for use in treating cancer.

The invention discloses a novel application of squamocin, and finds that the squamocin can effectively degrade histone methyltransferase EZH2 and MYC in head and neck squamous cell carcinoma (HNSCC), stomach cancer (GC) and colorectal cancer (CRC) cells and inhibit the cancer promoting transcriptional activity of the MYC. Compared with a medicine EPZ6438 which is sold on the market, the squimocin has higher capability of inhibiting the growth of HNSCC, GC and CRC (Cyclic Redundancy Chromatography). In mechanism, the squamocin enhances ubiquitination degradation related to endoplasmic reticulum stress, ubiquitin is triggered through E1 activating enzyme UBA6, ubiquitin is promoted to be transferred to E2 binding enzyme UBE2Z, and then degradation of EZH2 and MYC by E3 ligase FBXW7 is enhanced. The invention provides a novel application of the squamocin in clinical treatment of neck squamous cell carcinoma / gastric cancer / colorectum.

This invention discloses an NK cell-like inducer and its application. The NK cell-like inducer comprises a DNA methyltransferase inhibitor, a histone deacetase inhibitor, a histone methyltransferase inhibitor, and vitamin C or a derivative thereof; the final concentration of the DNA methyltransferase inhibitor is 0.05~0.45 μM; the final concentration of the histone deacetase inhibitor is 0.05~1 μM; and the final concentration of vitamin C or a derivative thereof is 1~1000 μM. The inducer combination of this invention can activate the synthesis of intracellular cryoprotective substances such as glutathione, effectively reducing cell damage during cryopreservation, and increasing the survival rate of NK cell-like cells after 7 days of liquid nitrogen cryopreservation to over 90%, thus achieving long-term storage of NK cell-like cells.

The present invention discloses a research and development method for histone methyltransferase Setdb1 in disuse osteoporosis, specifically including the steps of studying the diagnostic application of Setdb1 in disuse osteoporosis; studying the effect of Setdb1 on osteoblast proliferation function; studying the effect of bone-targeted delivery of si-Setdb1 on mouse bone formation and studying the effect of overexpression of Setdb1 on cell proliferation function in a 2D rotational MC3T3-E1 cell unloading model. This scheme found that the expression of histone methyltransferase Sedtb1 was significantly reduced in the 2D rotational cell unloading model and the mouse hindlimb tail suspension (HLU) unloading model, and explored its effect on osteoblast proliferation function and bone formation, suggesting that it may serve as a potential biomarker for disuse osteoporosis and can be used as a new target to combat disuse osteoporosis, with good prospects for translational medicine.

The present invention relates to novel therapeutic compositions and methods for treating cancer, in particular the use of proteinaceous inhibitors, including novel bicyclic peptide inhibitors, for use in the treatment of cancer.

This invention relates to a small molecule inhibitor of NSD2, its preparation method, and its applications. The NSD2 small molecule inhibitor is a compound with the structure shown in Formula (I) or a salt thereof: Formula (I). This NSD2 small molecule inhibitor exhibits high selectivity and potent efficacy against histone methyltransferase NDS2, and can be used to prepare drugs that inhibit NSD2, and drugs for the prevention and / or treatment of tumors or cancer.

The present invention belongs to the technical field of disease model construction, and particularly relates to a method for constructing a mouse model of chronic myeloid leukemia with conditional overexpression of human EZH2. The mouse model of chronic myeloid leukemia with conditional overexpression of human EZH2 constructed by the present invention finally obtains a mouse model in which the genes of Lyz2-creERT2, EZH2, BCR-ABL, and SCL-tTA are all positive and Lyz2-creERT2 and EZH2 are double homozygous through a series of hybridization and breeding processes, laying a solid research foundation for subsequent in-depth study of the role of histone methyltransferase EZH2 in the pathogenesis of chronic myeloid leukemia.

The invention relates to the technical field of stem cell engineering and anti-aging biology, in particular to a histone modification regulation method based on placenta amnion sub-totipotent stem cells and an anti-aging preparation thereof. The regulation and control method comprises the following steps: separating and purifying healthy full-month caesarean section placenta amniotic membrane tissues, carrying out composite enzymolysis and flow cytometry screening to obtain CD105 < + >, CD73 < + > and CD45 <-> stem cells, and primarily culturing the CD105 < + >, CD73 < + > and CD45 <-> stem cells; the method comprises the following steps: determining histone methyltransferase MLL3 and demethylase JMJD3 as target spots through ChIP-seq, and determining H3K4me3 and H3K27me3 as target modification sites; an MLL3 activator CM-272 with the final concentration of 15 [mu] M and a JMJD3 inhibitor GSK-J4 with the final concentration of 10 [mu] M form a composite regulator, and induction culture is performed for 84 h under the conditions of 37 DEG C and 5% CO2; and carrying out Western Blot verification and screening on the stem cells meeting the standard. According to the anti-aging preparation, regulated stem cells are used as active ingredients, a sodium alginate-gelatin (2: 1) composite carrier, 5% mannitol and 1% human serum albumin protective agent are used as auxiliary materials, and the injection with the pH of 7.2-7.4 is prepared. The method is accurate in regulation and control, and the preparation is remarkable in anti-aging effect and low in immunological rejection risk.

The application discloses a protein ZmTRX1 related to corn kernel development and application thereof, and focuses on genetic mechanism of corn kernel development. The application specifically discloses application of a protein, a substance for regulating gene expression of the protein or a substance for regulating activity or content of the protein in regulating plant kernel size and / or preparing a product for regulating plant kernel size and / or plant breeding and / or preparing a plant breeding product, wherein the protein is a protein shown in sequence 3 in a sequence table. The application finds and clones a corn histone methyltransferase gene ZmTRX1, and prepares two EMS mutant plant strains of the ZmTRX1 gene. The gene mutation leads to abnormal development of corn kernels, and the kernels are small and the hundred-grain weight is significantly reduced. The application provides a new clue for studying genetic characteristics of corn kernel development, promotes in-depth research on a molecular mechanism of corn kernel development, and provides a new gene resource for improving kernel size and crop yield.

The invention discloses a novel compound containing a biphenyl amide analogue structure and application of the novel compound, and belongs to the technical field of medicines. The compounds have a structural formula as shown in a general formula (I) or (II), and have remarkable EZH2 histone methyltransferase inhibitory activity as an anti-tumor drug. The invention also provides a preparation method of the compounds, a pharmaceutical composition containing the compounds and application of the pharmaceutical composition. The obtained novel compound containing the biphenyl amide analogue structure has better anti-tumor activity and safety, can be applied to EZH2, PRC2 and EZH2 / PRC2 mediated diseases, and particularly has great value as an anti-tumor agent. # imgabs0 #

The invention relates to the technical field of biology, in particular to a composition for treating platelet-related diseases and a preparation method thereof. The preparation method comprises the following steps: culturing initial cells by using a culture medium added with a small-molecule inhibitor, and collecting the obtained cells to obtain the composition, wherein the small-molecule inhibitor comprises a histone methyltransferase inhibitor, or comprises a combination of the histone methyltransferase inhibitor and a JAK kinase inhibitor; the starting cells are selected from one or more of total nucleated cells and mononuclear cells. The composition prepared by the preparation method can simultaneously realize in-vivo effects of timely supplement and relatively long-term continuous supply of platelets.

The invention belongs to the technical field of cell aging resistance, and particularly relates to a small molecule compound composition capable of reversing aging of adult stem cells and recovering regeneration activity of the adult stem cells, a method for reversing cell aging by using the chemical small molecule composition and application of the chemical small molecule composition. The composition capable of reversing cell senescence comprises a WNT / beta-catenin agonist, a TGF-beta receptor inhibitor, an RAR agonist, a Smooth receptor agonist, a VEGFR and PDGFR family multi-target inhibitor, a histone methyltransferase inhibitor and a JAK1 / 2 inhibitor, and effectively solves the problem of weak proliferation and regeneration potential of senescent adult stem cells. The aging of adult stem cells is effectively reversed, the original biological characteristics of the cells are maintained, and the clinical cell autotransplantation treatment and cell derivative treatment effects can be improved.

The application provides an application of vascular endothelial cell histone methyltransferase Ezh2 in preparation of a medicine for preventing and treating sepsis-associated encephalopathy and model construction, relates to the field of biomedical technology, and has the primary purpose of providing a drug target for preventing and treating SAE, namely, EZH2 in vascular endothelial cells. The application also provides an endothelial cell specific Ezh2 gene conditional knockout mouse model, the model has a high sensitivity and a high stability of BBB damage phenotype, and can be used for SAE pathogenesis research and drug screening. The application further has the purpose of providing SAE treatment drugs, diagnostic markers and screening methods based on the new target and the new model. In the application, a mouse Ezh2 gene conditional knockout and an induced conditional knockout-CLP high-sensitivity SAE model are successfully constructed. The model not only overcomes the problem of systemic knockout lethality, but also has a BBB damage and neuroinflammation phenotype which is much more serious and stable than that of a traditional CLP model, thereby providing an irreplaceable tool for drug research and development.

The present invention discloses an application of a histone methyltransferase SMYD2 in the preparation of a drug for preventing and treating restenosis caused by intimal regeneration after vascular injury. The prevention and treatment of restenosis caused by intimal regeneration after vascular injury is achieved by reducing the expression and activity of the histone methyltransferase SMYD2 in cells or tissues. By reducing the expression and activity of the histone methyltransferase SMYD2 in cells or tissues, the proliferation of smooth muscle cells is inhibited, and intimal regeneration is effectively inhibited. The drug can be used as a new target for preventing and treating diseases such as vascular stenosis, stenosis after stent surgery, and stenosis after endarterectomy.

The present invention provides a method for producing natural killer (NK) cells or precursor cells thereof from pluripotent stem cells, comprising a) a step of in vitro inducing hematopoietic progenitor cells (HPC) from pluripotent stem cells, b) a step of in vitro expanding HPC, and c) a step of in vitro inducing NK cells or precursor cells thereof from HPC and inhibiting histone methyltransferase and / or aromatic hydrocarbon receptors (AHR) in one or more of steps a) to c); and a method comprising (1) a step for forming pluripotent stem cell spheres having an average particle diameter of 200 [mu] m or more in a first culture medium, (2) a step for inducing the pluripotent stem cell spheres obtained in step (1) into a cell population containing HPC by three-dimensional culture using a second culture medium containing a histone methyltransferase inhibitor and / or an AHR antagonist, and (3) a step for inducing the pluripotent stem cell spheres obtained in step (2) into a cell population containing HPC. And (3) a step in which the cell population containing HPC obtained in step (2) is induced into a cell population containing NK cells or precursor cells thereof by three-dimensional culture using a third culture medium containing a histone methyltransferase inhibitor and / or an AHR antagonist, and one or more of steps (1) to (3) are performed by a perfusion culture method. Steps (1) to (3) are preferably performed by a continuous perfusion culture method.