71 results about "Histone methyltransferase" patented technology

The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK/ERK (mitogen-activated protein kinase/extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the reprogramming factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

The invention relates to the field of medicinal chemistry, in particular to a heterocyclic anthracene ketone histone methyltransferase inhibitor and a preparation method and application of the heterocyclic anthracene ketone histone methyltransferase inhibitor. It is proved by pharmacology experiments that the compound has a good inhibiting effect on histone methyltransferase from the molecular level to the cell level, has good antiproliferative activity on tumor cell strains and has reasonable medicinal parameters, such as a proper dissociation constant (pKa), a lipid-aqueous partition coefficient (LogD, pH=7.4), water solubility and film transmittance. It is testified by research on pharmacokinetics that the compound is wide in distribution in a body of a rat, the plasma clearance can be within an acceptable range, and good bioavailability is achieved. The compound and the pharmaceutic preparation of the compound can be used for treating a series of diseases caused by disorder of enzyme activity of the histone methyltransferase, such as solid tumor, leucocythemia, malaria and neurodegenerative diseases.

The present invention provides one new histone methyl transferase, HSPC069SET protein, polynucleotides coding the HSPC069SET protein, and recombinant technological process of generating the HSPC069SET protein. The present invention also discloses the use of polynucleotides coding this HSPC069SET protein. The HSPC069SET protein has histone methyl transferring function.

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 invention belongs to the technical field of medicinal chemistry, and in particular relates to acylhydrazone compounds with anti-tumor activity as well as a preparation method and application of the acylhydrazone compounds. The structures of the acylhydrazone compounds are as shown in a general formula (I) shown in the description, wherein R and R' are independently selected from any one or more of halogen, amino, cyano, alkoxy, 3,4-methylenedioxy, nitro, phenyl or substituted phenyl, and R and R' substituents are mono-substituted, disubstituted or tri-substituted. The preparation method issimple; biological activity test results of the compounds show that the compounds have a very good inhibitory effect on histone methyltransferase SET7, and have good application prospect in the development of anti-tumor aspects.

The invention relates to the technical field of medical treatment. The tea double-chlorine carboxamide and tea double-bromine carboxamide are newly synthesized compounds which can inhibit growths and invasions of cancer cells such as lung cancer, breast cancer, liver cancer, stomach cancer, colon cancer, prostate cancer, pancreatic cancer, cervical cancer, lymphoma, leukemia, and melanoma, and can obviously inhibit the tumor growth and metastasis in the body, and the inhibition effect of the compound is better than that of an anticancer medicament; the mechanism of action involves a receptor which is closely related to down-regulation and inhibition of the growth, invasion and metastasis of a tumor, signal transduction and regulation protein and kinase levels and a binding of a nuclear factor and DNA (Deoxyribonucleic Acid), and up-regulation of factors such as tumor suppressor proteins and cell cycle inhibitor proteins simultaneously; double tea chlorine carboxamide and double tea chlorine carboxamide can directly inhibit activities of histone deacetylase and histone methyltransferase EZH2(Enhancer Of Zeste Homolog 2) and the binding of the inflammatory factor NF-kB and DNA, and the activities of tea double-chlorine carboxamide and tea double-bromine carboxamide are better than that of the clinical anti-cancer medicament. The invention provides new applications of tea double-chlorine carboxamide and tea double-bromine carboxamide and intermediate compounds in preventing and treating the diseases such as cancers, inflammation, cardiovascular and immune deficiencies.

The invention relates to the technical field of medical treatment. Theanine nitrate aromatic amide is a newly synthetic compound, can inhibit the growth and invasion of such cancer cells as human lung cancer, breast cancer, liver cancer, gastric cancer, colon cancer, prostate cancer, pancreatic cancer, cervical cancer, lymphoma, leukemia and melanoma or the like, and can significantly inhibit tumor growth and metastasis in vivo, and the inhibitory effect of the theanine nitrate aromatic amide exceeds that of anticancer drugs; the action mechanism involves down-regulation of receptors closely related to inhibition of tumor growth, invasion and metastasis, regulation and control of protein and kinase levels and combination of a nuclear factor with DNA by signal transduction, and up-regulation of such factors as cancer suppressor protein and cell cycle inhibitory protein factor or the like; the theanine nitrate aromatic amide can directly inhibit the activity of histone deacetylase and histone methyltransferase EZH2 and the combination of an inflammatory factor NF-kappa B and DNA, and the activity of the nitrate fluorine aromatic amide exceeds that of the anticancer drugs. The invention provides a new use of the theanine nitrate aromatic amide in prevention and treatment of such diseases as tumor, inflammation, cardiovascular and cerebrovascular diseases and immunodeficiency, etc.

The invention discloses application of histone methyltransferase EZH2 to preparation of a medicinal preparation for preventing or treating aortic diseases. The invention confirms that the EZH2 can effectively inhibit autophagy of vascular smooth muscle cells and promote the survival of smooth muscle cells; a novel target spot and strategy are provided for effective treatment of aortic dissection and other aortic diseases with reduction of the vascular smooth muscle cells as the basis of cytology, and a basic is provided for the development of a novel medicament for treating diseases of the type.

The invention belongs to the field of biological gene engineering, and particularly relates to application of rice histone H3K36 methyltransferase in the aspects of enhancing drought resistance of rice and improving yield of a single plant. According to the application, a nucleotide sequence of rice histone H3K36 methyltransferase SDG708 is cloned, a recombinant expression vector is constructed, and transformation is carried out through an agrobacterium transformation method; by connecting a corn ubiquitin gene promoter, the SDG708 gene is continuously overexpressed in transgenic rice; and theSDG708 expression quantity down-regulation mutant is obtained by constructing an antisense RNA vector of a gene. A rice SDG708 overexpression transgenic plant shows obvious resistance under simulatedosmotic pressure stress, the plant resistance is also obviously improved under a soil drought condition, and the yield of a single rice plant can be obviously increased under normal and drought stress conditions. The application provides a high-quality gene and a breeding material for research on drought resistance and yield trait improvement of the rice, and has high practical application value.

An object of the present invention is to provide a technique for stably, inexpensively, and safely culturing stem cells having a differentiation ability while maintaining an undifferentiated state. The present invention relates to a medium for culturing stem cells, comprising at least one or more compounds selected from the group consisting of a ROCK inhibitor, a PKC inhibitor, a histone methyltransferase inhibitor, and a retinoic acid receptor agonist, and not containing a growth factor or having a low growth factor concentration; a method for culturing stem cells using the medium; a growth promoter for stem cell; as well as a cell composition containing stem cells or differentiated cells therefrom; and a method for producing the cell composition.

Inhibitors of HDAC and G9a inhibitors such as, for example, single compounds that inhibitor both HDAC and methyltransferase G9a (referred to herein as dual HDAC-G9a inhibitors, dual HDAC-G9a compounds, and dual HDAC-G9a inhibitor compounds) are described herein. For example, dual inhibitor compounds of Formulae I-III and methods of making and using thereof, are described herein. The dual inhibition activity of these compounds can provide inhibition of both histone deacetylase (HDAC) and histone methyltransferase G9a thereby providing anti-cancer effects.

The invention belongs to the technical field of plant transgenic engineering, and particularly relates to application of histone transmethylase gene in regulating and controlling a rice flowering period and a fringe type. The histone transmethylase gene SDG711 is obtain by cloning, and the nucleotide sequence is shown in SEQ ID NO: 1. Through the method of double-strand RNA inhibition, transformation rice corresponding to the histone transmethylase gene is obtained, the phenomenon that the flowering time of the plant is brought forward for about 2 weeks under a long-day condition after the histone transmethylase gene is inhibited is discovered, and the fringe type of the plant is much smaller than that of a wild plant. A detection to the modification condition of the transgenic histone of the transgene shows that the methylation and trimethylation levels of the histone H3K27 of the transgenic plant are obviously changed. By regulating and controlling the rice histone methylated modification and affecting the flowering time and fringe size of rice, the histone transmethylase gene SDG711 can affect the output of the rice.

The invention discloses a small-molecular compound combination and a method for inducing differentiated cells to prepare chondrocytes by using the small-molecular compound combination. The method is used for preparing the chondrocytes by directional induction of the differentiated cells. The directed induction includes inhibition of the activity of lysine deacetylase, inhibition of a signal pathway of TGF-beta, inhibition of the activity of PKC, inhibition of the activity of DNA methyltransferase, inhibition of the activity of histone methyltransferase, activation of a WNT/beta-catenin signalpathway, activation of a cAMP signal pathway and activation of an RA signal pathway; the small-molecular compound combination includes compounds for regulating and controlling the signal pathways and/or enzyme activities. Through phased induction of the small-molecular compounds, the differentiated cells can be differentiated into the chondrocytes, precision quality control can be achieved in eachstep, and standardization operation and large-scale production are facilitated. The method provided by the invention has wide donor sources, a patient himself can be used as a donor, and the chondrocytes needed for basic research, clinical treatment, or tissue engineering production can be obtained in a relatively short period of time.

An object of the present invention is to provide a method for preparing osteoblasts that are applicable, without causing risk of canceration, to bone defect repair or to the treatment of bone resorption, fracture, osteoporosis, or the like. To solve this problem, the present invention provides a method for preparing osteoblasts, the method comprising culturing mammal differentiated somatic cells in a medium in the presence of at least one compound selected from the group consisting of (1) statin compounds, (2) casein kinase 1 inhibitors, (3) cAMP inducers, and (4) histone methyltransferase inhibitors, to convert the somatic cells into osteoblasts.

The invention relates to the technical field of medical treatment. Theanine fluorine aromatic amide is a newly synthetic compound, can inhibit the growth and invasion of such cancer cells as human lung cancer, breast cancer, liver cancer, gastric cancer, colon cancer, prostate cancer, pancreatic cancer, cervical cancer, lymphoma, leukemia and melanoma or the like, and can significantly inhibit tumor growth and metastasis in vivo, and the inhibitory effect of the theanine fluorine aromatic amide exceeds that of anticancer drugs; the action mechanism involves down-regulation of receptors closely related to inhibition of tumor growth, invasion and metastasis, regulation and control of protein and kinase levels and combination of a nuclear factor with DNA by signal transduction, and up-regulation of such factors as cancer suppressor protein and cell cycle inhibitory protein factor or the like; the theanine fluorine aromatic amide can directly inhibit the activity of histone deacetylase and histone methyltransferase EZH2 and the combination of an inflammatory factor NF-kappa B and DNA, and the activity of the theanine fluorine aromatic amide exceeds that of the anticancer drugs. The invention provides a new use of the theanine fluoride aromatic amide in prevention and treatment of such diseases as tumor, inflammation, cardiovascular and cerebrovascular diseases and immunodeficiency, etc.

The invention provides application of an inhibitor of histone methyltransferase EZH2 to preparing medicine for controlling peritoneum fibrosis after peritoneal dialysis. The inhibitor of the histone methyltransferase EZH2 is 3-DZNeP. The 3-DZNeP is used for inhibiting the histone methyltransferase EZH2, the peritoneum pathology changes caused by exciting of a high-sugar peritoneal dialysis solution can be reduced, and the peritoneum function is improved. An inhibition mechanism inhibits a fibrosis signal channel, inhibits an inflammation signal channel, inhibits releasing of inflammation factors, and reduces angiogenesis. Therefore, the EZH2 can become an important target spot for controlling peritoneum fibrosis, and the inhibitor related to the EZH2 is expected to be clinical medicine forcontrolling occurrence of peritoneum fibrosis after peritoneal dialysis.

The invention discloses application of histone methyltransferase SDG723 in regulation of the heading period of rice, and belongs to the technical field of plant transgene engineering. Experiments show that in transgenic plants restraining the SDG723, H3K4 trimethylation drops significantly, and the fact that the gene is histone H3K4 trimethylation transferase is explained. After the SDG723 is restrained, the heading period of the plants is delayed by about 30 days. The genes related to the heading period are detected by using Realtime-PCR, and the expression quantity of the flowering promoting genes in the plants with the SDG723 restrained is reduced. The mentioned results explain the fact that the SDG723 regulates the heading period of the rice by regulating the H3K4 trimethylation modification.

The invention relates to a quinazoline hydroxamic acid derivative and a preparation method and application thereof. The structural formula of the quinazoline hydroxamic acid derivative is as shown informula I: Y is substituted or unsubstituted aliphatic hydrocarbon group or aromatic hydrocarbon group, R1 is a nitrogen-containing substituent group, and R2 and R3 are each independently hydrogen oran alkyl group. Researches show that the compound shown in the formula I has good inhibitory activity on histone methyltransferase and histone deacetylase, can effectively inhibit tumor cell proliferation, and can be used as a lead compound for research and development of antitumor drugs.