39 results about "DNA methyltransferase" patented technology

The application belongs to the field of chemical medicines, and particularly relates to a quinoline compound, a preparation method and use thereof and a pharmaceutical composition thereof. The application provides a quinoline compound shown in formula I, which has excellent DNA methyltransferase 1 (DNMT1) inhibitory activity and good selectivity, can be used as a novel DNMT1 inhibitor, and provides a new option for drug development and application of diseases driven by DNMT1. Formula I.

The application discloses a kind of small molecule compound combination and the method for preparing vascular endothelial cell using the small molecule compound combination induced differentiation cell.The method is directed to induce differentiated cell, and finally prepare vascular endothelial cell;The directional induction includes inhibiting the activity of lysine deacetylase, inhibiting the signal path of TGF-β, inhibiting the activity of DNA methyltransferase (DNMT), activating the signal path of WNT / β-catenin and activating the signal path of cAMP.The present application can be converted into vascular endothelial cell by small molecule compound combination induction, and each step can realize accurate quality control, which is convenient for standardized operation and large-scale production.The method provided by the present application has wide donor sources, and the patient himself can be used as a donor, so that the vascular endothelial cells required for basic research, clinical treatment or tissue engineering production can be obtained in a short time.

Disclosed are bifunctional compounds (degraders) comprising a [Targeting ligand]-[Linker]-[Degron] adduct, the targeting ligand comprising a substituted pyridine compound, the bifunctional compounds targeting the epigenetic writer protein deoxyribonucleic acid methyltransferase 1, which is responsible for the maintenance of DNA methylation during cell proliferation, for degradation. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat diseases and disorders characterized or mediated by aberrant DNMT1 activity.

The disclosure provides means, methods, and compositions of preventing, reducing, and treating kidney failure through the administration of fibroblasts, modified fibroblasts, and / or products derived from fibroblasts. The disclosure may also concern administration of fibroblasts prior to, concurrent with, or subsequent to administration of a nephrotoxic agent results in production of renal function. In some embodiments, fibroblasts are enhanced for augmentation of nephron-regenerative properties through culture under means including hypoxia, histone deacetylase inhibitor treatment, oxytocin, and / or DNA methyltransferase inhibitors.

Disclosed is a bifunctional compound (degradation agent) comprising a [targeting ligand]-[linker]-[degrader] adduct, the targeting ligand comprising a substituted pyridine compound, the bifunctional compound targeting an epigenetic writing protein desoxyribonucleic acid methyltransferase 1 responsible for maintaining DNA methylation during cell proliferation, for degradation. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of diseases and disorders characterized or mediated by aberrant DNMT1 activity.

The application discloses application of DNA methyltransferase inhibitors in preparation of drugs for treating polycystic kidney disease. Preferably, the DNA methyltransferase inhibitor is decitabine or azacitidine, and the polycystic kidney disease is polycystic kidney disease caused or aggravated by mTOR activation. The application uses Tsc2 knockout mouse embryo fibroblasts MEF and Tsc2 kidney-specific knockout mice, finds that after treatment of the DNA methyltransferase inhibitor decitabine, cell proliferation is inhibited, polycystic kidney disease of the mice is relieved, and kidney function is partially recovered. The application provides a new and effective technical means for treatment of polycystic kidney disease.

The invention relates to a phosphorus compound and an application thereof in an anti-tumor aspect. Specifically, the invention provides application of a compound as shown in a formula I, or an optical isomer, or a raceme, or a pharmaceutically acceptable salt thereof, the compound is used for preparing a composition or a preparation, and the composition or the preparation is used for preventing and / or treating tumors. The compound provided by the invention has low expression, no expression, low activity or no activity on mitochondrial membrane permeability conversion pores, low expression, no expression, low activity or no activity on peptidyl prolyl isomerase F, low expression or no expression on NNMT genes, high expression on DNA methylase, high expression on UHRF1, high methylation level on NNMT gene nucleotide sites, and low expression or no expression on NNMT genes. And / or the NNMT gene region DNA CpG site methylation level is high, so that the NNMT gene region DNA CpG site methylation level has a remarkable and excellent precise treatment effect on tumors. # imgabs0 #

This invention provides a novel compound that inhibits the activity of DNA methyltransferase 1 (DNMT1). [Solution] A compound of formula (I) or a prodrug thereof, or a pharmaceutically acceptable salt thereof is provided. TIFF2026136150000051.tif43160

[Problems] The object is to provide a compound as a therapeutic or prophylactic agent for TKI-resistant CML to replace the injection “Dacogen®” which has been clinically used as a therapeutic agent for high-risk myelodysplastic syndrome and acute myeloid leukemia. The said compound has remarkable stability against cytidine deaminase, a hydrolytic enzyme, and is absorbed in vivo even by oral administration, incorporated into the biosynthesis route of nucleic acid, and exhibits the effect of inhibiting DNA methyltransferase (DNMT).[Solutions] A prophylactic or therapeutic agent for TKI-resistant CML, comprising a compound represented by formula (I) or a salt thereof,wherein R1 and R2 are each independently a hydrogen atom or a silyl group represented by formula (II):wherein R3, R4, and R5 are each independently an alkyl group which may have a substituent, an aryl group which may have a substituent, or an arylalkyl group which may have a substituent, with the provision that the case where both R1 and R2 are hydrogen atom is excluded.

Disclosed are methods and systems for detecting methylation of the promoter of O-6-methylguanine-DNA methyltransferase gene (MGMT). In particular, the methods and systems may be utilized to detect methylation in the MGMT promoter in a DNA sample from a glioblastoma and optionally in order to predict whether a subject having the glioblastoma will respond to treatment with an alkylating agent. The methods and systems typically include a step of deep-sequencing the DNA sample after the DNA sample has been treated with a reagent that converts unmethylated cytosine to uracil such as a bisulfite reagent.

Pharmaceutical compositions and compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized an RNA aptamer are useful in methods of treating cancer (such as leukemia) and methods of inhibiting DNA methyltransferase. In embodiments, the RNA aptamer binds to an intracellular target such as DNMT1, NF-kB, RUNX1, MYC, MYB, ETS, PAX5, MDM2, F0XM1, PU.l, STAT3, STATS. STAT6, FAD, ATP5B, or beta-catenin.

This document describes methods and materials for treating cancer. In some cases, one or more diterpenoid epoxide compounds can be administered to a mammal (e.g., a human) having cancer to treat that mammal. For example, one or more diterpenoid epoxide compounds and one or more inhibitors (e.g., nucleoside-analog inhibitors) of a nucleoside DNA methyltransferase (DNMT) polypeptide can be administered to a mammal (e.g., a human) having cancer to treat that mammal.

The present invention provides a fusion protein and its application. The fusion protein comprises a histone binding module, a DNA methyltransferase 3α functional module, and a DNA methyltransferase 3β functional module. The fusion protein targets and binds to histone H3K27ac via the histone binding module, subsequently anchoring to cfDNA. The fusion protein then utilizes the DNA methyltransferase 3α and DNA methyltransferase 3β functional modules to catalyze the methylation of the 5' carbon position of cytosine in CpG sequences in cfDNA, thereby protecting the cfDNA through methylation.

The purpose of the present invention is to provide molecules that induce, in cells, the decomposition of proteins associated with epigenetic modification, particularly enzymes (e.g. DNA methyltransferase) that catalyze methylation of nucleic acids.　More specifically, the purpose of the present invention is to provide a compound represented by formula (I) or a salt thereof, or a solvate or a hydrate of the same. [In formula (I), A is a double-stranded nucleic acid and includes, in one strand, at least one 5'-CpG-3' sequence in which the 5-position of cytosine (C) has been methylated, the C of the 3'-GpC-5' that is complementary to said 5'-CpG-3' may be a modified base for covalently bonding DNMT1 to A, L is a hydrocarbon that may include oxygen, sulfur, phosphorus, or nitrogen, and B is a ligand molecule of an E3 ubiquitin ligase.]

The invention belongs to the field of plant molecular biology, and relates to application and a method of a vietnamese sophora root DNA methylase gene in improving cadmium stress tolerance of plants. The invention provides a DNA methylase gene StCMT1 from vietnamese sophora root, the nucleotide sequence of the DNA methylase gene StCMT1 is shown as SEQ ID No.2, and the amino acid sequence of an encoded protein is shown as SEQ ID No.1. According to the invention, by combining transcriptome screening with qRT-PCR verification, StCMT1 is determined as a key candidate gene for continuous inducible expression under cadmium stress; functional verification is carried out in tobacco, it is proved that overexpression of StCMT1 can enhance cadmium resistance under the stress conditions of 100 [mu] M and 200 [mu] M CdCl2, and definite repeatability and application value are achieved. The method can be used for constructing cadmium-resistant plant materials and cultivating cadmium-resistant varieties, and a new molecular target and technical scheme are provided for safe production of cadmium-contaminated soil and quality improvement of medicinal plants.

The invention belongs to the field of medicines, and relates to a quinoline derivative as well as a preparation method and application thereof. The quinoline derivative is selected from at least one compound in a structure as shown in a formula I, or a tautomer or a mixture thereof, or a prodrug thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof. A DNA methyltransferase inhibitory activity test, a histone deacetylase inhibitory activity test and a tumor cell proliferation inhibitory activity test on the compound provided by the invention prove that the quinoline derivative provided by the invention is a potential antitumor drug with inhibitory activity on DNA methyltransferase and histone deacetylase. The raw materials of the compound are easy to obtain, the preparation method is simple, and experiments prove that the compound has a good anti-cancer effect and has a good application prospect in the field of design, research and development of anti-tumor drugs.

The present invention relates to a phosphorus compound and the anti-tumor use thereof. Specifically, provided in the present invention is use of a compound of formula I, or an optical isomer thereof, or a racemate thereof, or a pharmaceutically acceptable salt thereof, or a deuterated compound thereof, in preparing a composition or a formulation, the composition or the formulation being used for preventing and / or treating tumors. The compound of the present invention exhibits excellent precise therapeutic efficacy against tumors characterized by low expression, no expression, low activity or inactivity of mitochondrial permeability transition pores, low expression, no expression, low activity or inactivity of peptidylprolyl isomerase F, low expression or no expression of NNMT gene, high expression of DNA methyltransferase, high expression of UHRF1, high methylation levels at nucleotide sites of the NNMT gene, and / or high methylation levels at DNA CpG sites in an NNMT gene region.

The invention discloses an epigenetic modification editor for targeted addition of DNA methylation and application of the epigenetic modification editor, and belongs to the technical field of biology. The epigenetic modification editor for targeted addition of DNA methylation, provided by the invention, comprises a fusion protein of CRISPR / dCas9 related protein and n copies of yeast transcription activator GCN4 peptide fragments and a fusion protein of a single-chain antibody scFv and a tobacco DNA methyltransferase catalytic structural domain DRM2, and can be combined with guide RNA to efficiently and accurately add DNA methylation to a target position.

The invention provides a fusion protein and application thereof. The fusion protein comprises a histone binding module, a DNA methyltransferase 3 alpha functional module and a DNA methyltransferase 3 beta functional module. The fusion protein targets and is combined with histone H3K27ac through a histone binding module, then cfDNA is anchored, methylation of cytosine 5'carbon position of a CpG sequence in the cfDNA is catalyzed through a DNA methyltransferase 3 alpha functional module and a DNA methyltransferase 3 beta functional module, and the protection effect on the cfDNA is achieved through methylation.

The invention discloses a preparation method of a spherical DNA nano machine for detecting O6-methylguanine-DNA methyltransferase (MGMT) and application of the spherical DNA nano machine in detection of the expression level of tumor cells MGMT. The method comprises the following steps: firstly, designing a DNA walker with MGMT recognition and signal amplification functions, and fixing the DNA walker on the surface of a gold nanosphere through sulfydryl modification to construct a spherical DNA nanomachine; when the MGMT interacts with a DNA Walker chain, a methylated basic group G on DNA enzyme can be repaired, so that the activity of the DNA enzyme is recovered, an enzyme digestion reaction is initiated, a Track chain marked with a fluorophore is broken and released, a fluorescence signal change is generated, and high-sensitivity detection of the MGMT is realized. The method can effectively detect the MGMT protein in a low concentration range, and has a good biomedical application prospect.

The invention provides a poplar DNA methyltransferase CMT3, a coding gene and application of the poplar DNA methyltransferase CMT3 in cultivation of improved forest plants, and belongs to the technical field of molecular breeding. The invention provides a poplar DNA methyltransferase CMT3. The amino acid sequence of the poplar DNA methyltransferase CMT3 is as shown in SEQ ID NO: 1. The poplar DNA methyltransferase CMT3 can improve the wood quality of plants through negative regulation and control, and can inhibit the plant height and ground diameter of the plants through negative regulation and control. According to the embodiment of the invention, the quality difference between a PagCMT3 gene knockout strain and wild type wood is compared, and the result shows that the knockout of the PagCMT3 gene can promote the expansion of cells and the thickening of secondary cell walls and change the property of the wood, so that an improved forest variety with thickened secondary cell walls and enlarged cells is obtained, and the quality of the wood is improved. The method is of great significance to genetic engineering breeding of woody plants.

The invention discloses application of RG108 in heart transplantation immunosuppression by regulating T cell functions, and relates to the technical field of medical bioengineering. The invention innovatively provides a method for inhibiting the activity of DNA methyltransferase 1 (DNMT1) by using a small molecule compound RG108, and by reducing the methylation level of a CDKN1A gene promoter, restoring the expression of the promoter and inducing T cells to enter an aging state, the proliferation and effect activity of the promoter is reduced, and rejection reaction is inhibited. The RG108 is a non-nucleoside DNMT1 selective inhibitor with a clear structure, the activity of the inhibitor is inhibited by combining with a catalytic structural domain, DNA is not doped, off-target toxicity is not caused, and the RG108 is an ideal molecule for realizing controllable and reversible epigenetic regulation. A new transplantation immune tolerance strategy is established, and the defects that an existing immunosuppressor is large in side effect and cannot induce immune memory tolerance are overcome.

The invention discloses application of a DNA (deoxyribonucleic acid) methyltransferase gene DMT2 in regulating and controlling salt resistance of poplars. An sgRNA expression cassette is designed for a DNA methyltransferase gene DMT2 by virtue of a CRISPR / Cas9 gene editing technology and is constructed on a knockout vector, and poplar is transformed by virtue of an agrobacterium-mediated method, so that a transgenic plant is obtained. Further experiments show that after the DNA methyltransferase gene DMT2 is knocked out of the poplar, the salt stress resistance of the poplar is enhanced, and the poplar can cope with adverse stress environments such as salt and alkali, so that the method disclosed by the invention can be applied to the fields such as planting of saline-alkali tolerant forest trees.

The disclosure provides means, methods, and compositions of preventing, reducing, and treating kidney failure through the administration of fibroblasts, modified fibroblasts, and / or products derived from fibroblasts. The disclosure may also concern administration of fibroblasts prior to, concurrent with, or subsequent to administration of a nephrotoxic agent results in production of renal function. In some embodiments, fibroblasts are enhanced for augmentation of nephron-regenerative properties through culture under means including hypoxia, histone deacetylase inhibitor treatment, oxytocin, and / or DNA methyltransferase inhibitors.

The present disclosure relates to methods for treating a tumor (or cancer) in a subject in need thereof, the tumor comprising an unmethylated MGMT promoter. In some embodiments, the method comprises administering to the subject an anti-cancer treatment comprising an IL-7 protein, alone or in combination with an additional therapeutic agent (e.g., chemotherapy). Some embodiments of the present disclosure relate to methods for identifying a cancer subject (e.g., having glioblastoma) suitable for anti-cancer treatment. Provided herein is a method for treating a tumor in a subject in need thereof, the method comprising administering to the subject an anti-cancer treatment, wherein a tumor sample obtained from the subject contains unmethylated MGMT promoter. 6 -methylguanine-DNA methyltransferase (MGMT) promoter and the anti-cancer treatment comprises interleukin-7 (IL-7) protein.

An isolated polynucleotide encoding a fusion protein which comprises a DNA targeting moiety linked to a catalytic domain of a plant DNA methyltransferase 3 (DNMT3) protein is disclosed. Uses thereof are also disclosed.

The invention belongs to the technical field of cancer treatment, and discloses application of co-targeting EZH2 / DNMT to synergistically reversing castration-resistant prostate cancer resistance. We prove that dual targeting of DNMT and EZH2 breaks epigenetic transformation, so that tumors are re-sensitive to androgen deprivation therapy. The strategy not only eliminates CRPC in a preclinical model, but also reverses immunosuppression, so that cytotoxic T cell infiltration is increased by 11.4 times. We data extend the use of EZH2 inhibitors beyond PRC2 dependent cancers, localizing the interaction of DNA methyltransferase with EZH2 as a targeting weakness in extracellular matrix rich solid tumors. The combination therapy provides a mandatory solution to overcome stromal disorders, which provides a revolutionary strategy for biomechanical factor driven malignancies.

This invention belongs to the field of animal cell culture technology, specifically relating to a cytokine-free human pluripotent stem cell culture medium. The technical problem this invention aims to solve is that the cytokines used in existing pluripotent stem cell culture media are expensive and easily degraded during the culture process. This invention provides a cytokine-free human pluripotent stem cell culture medium, comprising a basal medium, a spleen tyrosine kinase SYK inhibitor, and a non-covalent inhibitor of DNA methyltransferase Dnmt1. This culture medium has a simple and well-defined composition; two small chemical molecules (R406, GSK3484862) replace traditional cytokines (FGF2, TGFB), enabling effective expansion of pluripotent stem cells in vitro and maintaining their differentiation capacity.

The present invention belongs to the field of chemical drugs, and discloses a quinazoline derivative, a preparation method thereof, a pharmaceutical composition and an application. The present invention obtains a novel quinazoline derivative as shown in Formula I. The preparation process is simple and feasible, and a variety of quinazoline derivatives are obtained by a sub-pathway method. It can be applied to the preparation of DNA methyltransferase 1 inhibitors, and can form a pharmaceutical composition, which has a certain inhibitory effect on the proliferation of a variety of tumor cells and is suitable for the development of drugs for treating leukemia and myelodysplastic syndrome. Formula I.

The application discloses application of DNMT3B as a marker in preparation of a severe EV71 infection diagnosis product, and belongs to the biomedical field. It is found by the application that the nucleocytolysis degree and ubiquitination level of DNA methyltransferase DNMT3B can be used for diagnosing children with severe EV71 infection. EV71 infection promotes partial transport of DNMT3B in the cell nucleus to the cytoplasm, and promotes K63 ubiquitination modification of DNMT3B by combining the 3C and 3D proteins with DNMT3B, so that DNMT3B is finally degraded by a proteasome. The reagent for detecting the nucleocytolysis degree of DNMT3B and / or the reagent for detecting the ubiquitination level of DNMT3B can be used for preparing a severe EV71 infection diagnosis product or a severe EV71 infection prognosis diagnosis product, so as to realize diagnosis of severe EV71 infection or prognosis thereof.