27 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.

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.

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.

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.

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 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 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 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 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.

The invention discloses a research method of a DNA (Deoxyribose Nucleic Acid) methylated transferase regulation mechanism of oligodendrocyte myelin sheath abnormality, and belongs to the technical field of detection research. The method comprises the following steps: S1, constructing a gene knockout mouse and a gene overexpression mouse through a gene editing technology, and setting a normal mouse as a control group; s2, separating and culturing the oligodendroglia cells; and S3, detecting the activity of the methylated transferase, the DNA methylation level and the myelin sheath index of the oligodendroglia cells. The invention focuses on a brand-new research method of a DNA methylated transferase regulation mechanism aiming at oligodendrocyte myelin sheath abnormality, and aims at deeper and more accurate analysis of the regulation mechanism by taking a mouse as an experimental model. According to the method, advanced molecular biology technology, cell biology technology and bioinformatics analysis means are integrated, and a set of comprehensive and systematic solution is provided for related research.

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

Malignant glioma has a poor prognosis, despite current therapeutic modalities. Standard of care therapy consists of surgical resection, fractionated radiotherapy concurrently administered with temozolomide (TMZ), a DNA-alkylating chemotherapeutic agent, followed by adjuvant cycles of TMZ. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair enzyme which removes alkylated lesions from tumor DNA, thereby promoting chemoresistance. MGMT promoter methylation is a known predictor of temozolomide responsiveness; patients with unmethylated MGMT have a poorer prognosis. We employed deactivated Cas9-CRISPR technology to effectively target methylation in the vicinity of the MGMT methylation-specific polymerase chain reaction (MSP) region, as mediated by the catalytic domain of DNA methyltransferase DNMT3A. In doing so, we discovered that the selected dCas9 / CRISPR-mediated methylation of certain regions of MGMT gene sequences can be used to enhance chemosensitivity in malignant glioma cells.

Provided herein are engineered epigenetic effectors, such as DNA methyltransferases and methylcytosine dioxygenases that are smaller than their naturally occurring counterparts. The engineered epigenetic effectors find use in regulating expression level of target genes in a cell, e.g., when targeted to a genetic locus of interest by a targeting moiety, such as a Cas protein, coupled thereto.

The application belongs to the technical field of medicines, and particularly relates to a compound with inhibitory activity on DNA methyltransferase 1 (DNMT1) and a preparation method and application thereof. In the application, a DNMT1 small-molecule inhibitor with a 2-isoindole-3-carbazolyl propionic acid skeleton is found and prepared, and is expected to be applied to the treatment of diseases related to DNA hypermethylation, especially tumor treatment.

Provided are fusion proteins and DNA-targeting systems for targeted transcriptional repression comprising an effector domain comprising engineered DNA methyltransferase 3 proteins or portions thereof, such as DNA methyltransferase 3L proteins or portions thereof. In some aspects, the compositions and methods provided herein facilitate targeted transcriptional repression by targeting the effector domain to a target site, such as a target site for a target gene. Also provided are methods and uses related to the provided fusion proteins, for example in connection with therapeutic applications.

The invention discloses a method for improving cadmium resistance of gynostemma pentaphyllum and reducing cadmium accumulation through 5-azacytidine and application, and belongs to the technical field of plant cultivation and epigenetic regulation. In order to solve the problems that the growth of the gynostemma pentaphylla is inhibited and the cadmium content of the overground part exceeds the standard due to cadmium pollution, 5-azacytidine and CdCl2 are applied in a water culture stage for composite stress treatment, the 5-azacytidine is used for inhibiting the activity of DNA methyltransferase and reducing the methylation level of genomic DNA, so that the expression of a cadmium transport gene is regulated and controlled, and the cadmium content of the overground part is reduced. Transferring of cadmium to the overground part is inhibited, and enrichment of cadmium in the root system is promoted; meanwhile, an antioxidant enzyme system is activated, oxidative damage is relieved, and saponin synthesis is promoted. The method is mainly used for cultivating gynostemma pentaphyllum in a cadmium-polluted environment, so that the cadmium resistance of the gynostemma pentaphyllum is enhanced, the cadmium content of medicinal parts is reduced, and the safety and quality of medicinal materials are guaranteed.