82 results about "Methyltransferase inhibitor" patented technology

The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

The present invention provides methods of ameliorating or reducing the extent of ischemic injury, reperfusion injury, and myocardial infarction, by administering an inhibitor of histone deacetylase enzyme (HDAC) or an inhibitor of DNA methyltransferase enzyme (DNMT).

There is disclosed a methylated intermediate which may be demethylated to provide an inhibitor of catechol-O-methyltransferase useful in the treatment of Parkinson's disease. Also disclosed are methods of making and using said intermediate.

The present invention relates to a pharmaceutical composition for treating a neoplasm, a preneoplasm, a proliferative disorder and / or a precancerous lesion, the use of such compositions for the treatment of the listed conditions, and methods of treating the listed conditions. The composition of the present invention comprises an inhibitor of eIF4E, a methltransferase inhibitor, and a pharmaceutically acceptable carrier.

Methods and compositions are provided for treating myelodysplastic syndrome and acute myeloid leukemia, wherein the composition comprises at least one compound according to Formula I:wherein R1 is selected from the group consisting of —NH2, —NH—CH2—CO2H, —NH—CH(CH3)—CO2H, and —NH—C(CH3)2—CO2H, or a pharmaceutically acceptable salt of such a compound; and a DNA methyltransferase inhibitor, or a pharmaceutically acceptable salt thereof.

Provided herein, in part, is a method of treating a neurological or movement disorder in a patient in need thereof, comprising subcutaneously administering to said patient a pharmaceutically acceptable composition comprising levodopa and optionally carbidopa and optionally entacapone or tolcapone, or pharmaceutically acceptable salts thereof, wherein said composition is administered substantially continuously, and compositions that can be used in the disclosed methods.

Provided herein, in part, is a method of treating a neurological or movement disorder in a patient in need thereof, comprising subcutaneously administering to said patient a pharmaceutically acceptable composition comprising levodopa and optionally carbidopa and optionally entacapone or tolcapone, or pharmaceutically acceptable salts thereof, wherein said composition is administered substantially continuously, and compositions that can be used in the disclosed methods.

The invention relates to a method for detecting DAN methyltransferase activity based on strand displacement amplification and DNAzyme amplification. A three-function double-stranded DNA probe is designed. Methylation happening to the three-function double-stranded DNA probe is specifically recognized through DAN methyltransferase. Remaining non-methylated double-stranded DNA is specifically cut through HpaII restriction enzymes, methylated double-stranded DNA triggers a strand displacement reaction, a large amount of 8-17 DNAzyme is released, the 8-17 DNAzyme catalyzes cutting of a large number of hairpin-line molecular beacon substrates, and remarkable fluorescent enhancement is triggered. The method can sensitively detect the DAN methyltransferase activity, and the detection limit is 0.0082 U / mL. The method has potential application in research of influences of anti-cancer drugs on DAN methyltransferase activity inhibition and screening of DAN methyltransferase inhibitors.

There is disclosed a methylated intermediate which may be demethylated to provide an inhibitor of catechol-O-methyltransferase useful in the treatment of Parkinson's disease. Also disclosed are methods of making and using said intermediate.

The invention discloses an umbilical cord blood Treg cell in-vitro amplification method based on trophoblastic cells and application. The specific technical method comprises the steps that firstly, umbilical cord Wharton's jelly mesenchymal stem cells are adopted as the trophoblastic cells to induce preliminary proliferation of Treg cells in umbilical cord blood mononuclear cells; then, pure Tregcells are obtained through magnetic bead sorting; and finally, the Treg cells are stimulated to be rapidly amplified by using optimized amplification factors. According to the amplification method, human AB plasma, IL-2, rapamycin, an RARA agonist and a DNA methyltransferase inhibitor are used as the optimized amplification factors, and a large number of umbilical cord blood Treg cells with high purity and high activity can be prepared within two weeks. Umbilical cord blood is used as a raw material for Treg cell amplification, batch preparation can be achieved, and Treg cell quality fluctuation caused by individual differences of samples can be reduced. The umbilical cord blood Treg cells have low immunogenicity and can be used as universal cells for clinical research, such as autoimmunediseases, graft-versus-host diseases and the like.

Methods and compositions are provided for treating myelodysplastic syndrome and acute myeloid leukemia, wherein the composition comprises at least one compound according to Formula I:wherein R1 is selected from the group consisting of —NH2, —NH—CH2—CO2H, —NH—CH(CH3)—CO2H, and —NH—C(CH3)2—CO2H, or a pharmaceutically acceptable salt of such a compound; and a DNA methyltransferase inhibitor, or a pharmaceutically acceptable salt thereof.

The present invention provides isolated nucleic acids encoding delta DNA methyltransferase 3B molecules that are involved in the treatment and prevention of cancers such as, but not limited to, lung cancer. The delta DNA methyltransferase 3B molecules of the present invention are found to play a critical role in promoter-specific methylation of tumor suppressor genes. The DNA methyltransferase 3B molecules of the present invention are provided as therapeutic targets for identifying inhibitors of DNA methyltransferase. Such inhibitors are contemplated for the treatment and / or prevention of cancers. In particular embodiments, the present invention involves the treatment and prevention of a non-small cell lung cancer.

Methods for treating and / or preventing disease conditions caused or induced or aggravated by microbes, especially bacteria, by inhibiting DNA methyltransferase activity, such as by administering to an animal a DNA methyltransferase inhibitor, are disclosed, along with methods of reducing or ablating virulence in bacteria by inhibiting DNA methyltransferase activity.

There is disclosed a methylated intermediate which may be demethylated to provide an inhibitor of catechol-O-methyltransferase useful in the treatment of Parkinson's disease. Also disclosed are methods of making and using said intermediate.

The invention discloses a long-chain non-coding RNA marker for assisting diagnosis of esophageal squamous cell carcinoma (ESCC). The long-chain non-coding RNA is LINC01419, the expression amount of the long-chain non-coding RNA is detected and can be used for auxiliary diagnosis or prediction of the esophageal squamous cell carcinoma, and the methylation status of a GSTP1 gene is monitored to predict the sensitivity of the esophageal squamous cell carcinoma to 5-FU chemotherapy. The expression level of a LINC01419 gene can be detected by an RT-PCR, real-time quantitative PCR, immunoassay, in situ hybridization, a chip or a high-throughput sequencing platform. The invention further discloses application of a methyltransferase inhibitor 5-Aza-CdR to regulate the expression of the long-chainnon-coding RNA LINC01419 and response to the 5-FU, and application of an inhibitor medicine including the long-chain non-coding RNA LINC01419 in treatment of the esophageal squamous cell carcinoma. The molecular marker of the esophageal squamous cell carcinoma is provided, a theoretical basis for mechanism research and clinical individualized treatment of the esophageal squamous cell carcinoma isprovided, and by monitoring the overexpression of the LINC01419 in the ESCC, a new treatment strategy for the clinical treatment of the ESCC can be provided.

Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a cyclin-dependent kinase inhibitor and a DNA methyltransferase inhibitor to a mammal in need thereof.

The invention discloses an application of vanillin in preparation of a nicotinamide-N-methyltransferase inhibitor. The inhibitor is prepared from traditional Chinese medicine monomer vanillin and pharmaceutically acceptable auxiliary materials. According to the invention, proliferation of various colorectal cancer cell strains is inhibited by inhibiting the expression of NNMT and enzyme activity in vitro and vivo, and an anti-tumor effect is achieved. Studies show that vanillin can weaken the drug resistance of colorectal cancer cell strains to 5-FU caused by high expression of NNMT in vitro,so that the chemotherapy sensitivity is enhanced; the apoptosis of the colorectal cancer cell strains with high expression of NNMT is increased by inducing ROS production and mitochondrial damage in cells; and the inhibitory effect of 5-fluorouracil on tumor proliferation and the apoptosis rate can be improved, so as to enhance the chemotherapy effect. The vanillin can be used as an NNMT inhibitorfor preparing anti-colorectal cancer drugs or adjuvant chemotherapy drugs, and has a good application prospect.

The invention provides a method for preparing licochalcone A. The method comprises the following steps: culturing glycyrrhiza inflata hairy roots or glycyrrhiza inflata seedlings in a culture medium containing a DNA methyltransferase inhibitor for not less than three days, collecting roots of the glycyrrhiza inflata hairy roots or glycyrrhiza inflata seedlings, and extracting the licochalcone A. The culture medium containing the DNA methyltransferase inhibitor is used for culturing glycyrrhiza inflate seedlings or glycyrrhiza inflate hairy roots, so that the DNA methylation degree of the glycyrrhiza inflate seedlings or glycyrrhiza inflate hairy roots can be reduced; and genes which are originally silent or low in expression quantity and are beneficial to accumulation of licochalcone A are reactivated, so that the content of licochalcone A is quickly and effectively increased.

The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

A first aspect of the invention relates to a combination comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof. A second aspect of the invention relates to a pharmaceutical product comprising a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect of the invention relates to a method of treating a proliferative disorder, said method comprising simultaneously, sequentially or separately administering a DNA methyltransferase inhibitor and 1-(2-C-cyano-2-dioxy-β-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine, or a metabolite thereof, to a subject.

The invention discloses a pharmaceutical composition and uses thereof. The pharmaceutical composition comprises a DNA methyltransferase inhibitor and a histone deacetylase inhibitor. The invention also discloses new uses of the pharmaceutical composition. The pharmaceutical composition is used to treat tumor cells together to obtain an exosomes tumor vaccine. The invention also discloses a method for preparing a tumor vaccine by using the pharmaceutical composition. The method comprises the following steps of using procaine and MS-275 to treat the tumor cells, and separating and purifying exosomes secreted by the tumor cells. The pharmaceutical composition disclosed by the invention improves the therapeutic effect of the exosomes tumor vaccine, and has an important clinical application value.

The invention relates to a method for synthesizing an EZH2 methyltransferase inhibitor GSK126, and belongs to the field of medicinal chemistry. EZH2 is highly expressed in various malignant tumors and is expected to provide a new target for tumor therapy; GSK126 can effectively inhibit the activity of an EZH2 methyltransferase, thereby arousing the interest of people in research. According to the method provided by the invention, the reaction steps are simplified, and by using a chiral introduction method, the chiral separation link in the literature is avoided, and the synthesizing cost is reduced.

The invention belongs to the field of medicinal chemistry, and relates to a fluorine-substituted monocarbazole derivative. The fluorine-substituted monocarbazole derivative is one or more of compoundsrepresented by formula (I) and formula (II), or one or more of medically acceptable soluble salts formed by the compounds of the formula (I) and the formula (II). The fluorine-substituted monocarbazole derivative obtained by the invention can be used for preparing a DNA methyltransferase inhibitor or a histone demethylase inhibitor. The fluorine-substituted monocarbazole derivative has an inhibiting effect on proliferation of cancer cells and can be used for preparing medicines for treating and / or preventing cancers. An in-vitro cancer cell proliferation inhibition test shows that the fluorine-substituted monocarbazole compound has anti-proliferative activity on human lung cancer cells (A549), human colon cancer cells (HCT116), human gastric cancer cells (MNK-45), human liver cancer cells(HepG2), RPMI-8226 and Karpas 299.

Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a cyclin-dependent kinase inhibitor and a DNA methyltransferase inhibitor to a mammal in need thereof.

The invention relates to the treatment of cancer using DNA damaging agents. The invention provides methods for treating a mammal with cancer, the method comprising inhibiting in the mammal acidic residue methyltransferase (Arm1) in combination with administering to the mammal a DNA damaging agent. The invention further provides pharmaceutical formulations comprising an inhibitor of acidic residue methyltransferase (Arm1) and a DNA damaging agent.

The invention provides an SET8 lysine methyltransferase inhibitor, an intermediate, a preparation method and applications thereof, wherein the structural general formula of the inhibitor is represented in the specification, and the inhibitor has remarkable inhibition activity on SET8 lysine methyltransferase, has remarkable in-vitro anti-tumor activity, and can be further developed into a targetedanti-tumor drug taking SET8 as a target.

The invention provides an SET8 lysine methyltransferase inhibitor as well as a preparation method and application thereof. The inhibitor has a structural formula shown in the description. The inhibitor provided by the invention has a remarkable inhibition function on SET8 lysine methyltransferase, and in addition, has a remarkable inhibition effect on proliferation of tumor cells.

The invention provides an SET8 lysine methyltransferase inhibitor and an intermediate, a preparation method and application thereof. The structural general formula of the inhibitor is shown as follows. The inhibitor has a remarkable inhibition activity on SET8 lysine methyltransferase, meanwhile has a noticeable in-vitro anti-tumor activity and can be further developed into a targeted anti-tumor drug with SET8 being a target.