33 results about "DNA Methyltransferase Inhibitor" patented technology

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 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.

Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR 109 ligands include, but are not limited to butyrate, β-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2′-deoxytidine, 1-β-D-arabinfαmosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR 109 ligand serum blood level of about 1 to about 1000 μM. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.

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.

Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR109 ligands include, but are not limited to butyrate, β-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2′-deoxytidine, 1-β-D-arabinfarnosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR109 ligand serum blood level of about 1 to about 1000 μM. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.

The present invention relates to a method of testing whether a patient suffering from multiple myeloma will respond or not to a combination treatment consisting of at least one histone deacetylase inhibitor (HDACi) with at least one DNA methyltransferase inhibitors (DNMTi) comprising: i) determining the expression level (ELi) of several genes G1-Gn selected from table A in a biological sample obtained from said patient ii) comparing the expression level (ELi) determined at step i) with a predetermined reference level (ELRi) iii) calculating the HADMS score trough the following formula (I) wherein βi represent the regression β coefficient reference value for the gene Gi and Ci=1 if the expression of the gene Gi (ELi) is higher than the predetermined reference level (ELRi) or Ci=−1 if the expression of the gene (ELi) is lower than or equal to the predetermined reference level (ELRi) iv) comparing the score HADMS determined at step iii) with a predetermined reference value HADMSR v) and concluding that the patient will respond to the combination treatment when the HADMS score is higher than the predetermined reference value HADMSR or concluding that the patient will not respond to the combination treatment when the HADMS score is lower than the predetermined reference value HADMSR.H⁢⁢A⁢⁢D⁢⁢M⁢⁢S=∑i=1n⁢β⁢⁢i×Ci(I)

The present disclosure provides a method of treating a neurodegenerative disorder, the method comprising administering a DNA methyltransferase inhibitor.

The invention discloses a fluorine-substituted bimolecular carbazole derivative represented by formula (I) or a pharmaceutically acceptable salt thereof, R 1 , R 2 , R 3 , R 4 , R 5 as defined in the specification. The fluorine-substituted bimolecular carbazole derivatives provided by the present invention or their pharmaceutically acceptable salts can be used to prepare DNA methyltransferase inhibitors or histone demethylase inhibitors, which are confirmed by in vitro cancer cell anti-proliferation tests, The fluorine-substituted bimolecular carbazole derivative of the present invention has anti-proliferation activity on cancer cells.

The invention discloses a method for improving the biomass and carotenoid content of Chlamydomonas reinhardtii by using a DNA methyltransferase inhibitor, and belongs to the field of food science andtechnology. According to the method, after the Chlamydomonas reinhardtii cells are cultured in a liquid medium containing a DNA methyltransferase inhibitor for a certain period of time, the biomass ismonitored, the algae cells are collected and the pigments are extracted every day. The method of the invention is simple and feasible, has a good effect, is convenient to operate, and can help quickly and effectively improve the biomass and carotenoid content of Chlamydomonas reinhardtii after adding of the DNA methyltransferase inhibitor. In the invention, the dosage of the DNA methyltransferaseinhibitor is very small, the effect is remarkable, and the operation is convenient.

The invention belongs to the field of medicinal chemistry and relates to a fluorine-substituted monocarbazole derivative, which is one or more of the compounds shown in formula (I) and formula (II), or formula (I) or formula (II) One or more of the medically acceptable soluble salts formed by the indicated compounds. The fluorine-substituted monocarbazole derivatives obtained in the present application can be used to prepare DNA methyltransferase inhibitors or histone demethylase inhibitors. The fluorine-substituted monocarbazole derivatives of the invention have inhibitory effect on the proliferation of cancer cells and can be used to prepare medicines for treating and / or preventing cancer. The in vitro cancer cell proliferation inhibition test shows that the fluorine-substituted monocarbazole compounds obtained in the present invention exhibit inhibitory effects on human lung cancer cells (A549), human colon cancer cells (HCT116), human gastric cancer cells (MNK-45), human liver cancer Antiproliferative activity of cells (HepG2), RPMI‑8226 and Karpas 299.

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.

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 an in vitro amplification method and application of umbilical cord blood Treg cells based on trophoblast cells. The specific technical method is as follows: firstly, using umbilical cord Wharton's jelly mesenchymal stem cells as trophoblast cells to induce Treg in umbilical cord blood mononuclear cells Initial proliferation of cells; then purer Treg cells were obtained by magnetic bead sorting; finally, optimized expansion factors were used to stimulate the rapid expansion of Treg cells. The present invention adopts human AB plasma, IL-2, rapamycin, RARA agonist and DNA methyltransferase inhibitor as optimized amplification factors, and can prepare a large amount, high purity and high activity within 2 weeks. Strong cord blood Treg cells. Using umbilical cord blood as the raw material for Treg cell expansion can be prepared in batches, and can reduce the quality fluctuation of Treg cells caused by individual differences in samples. Umbilical cord blood Treg cells have low immunogenicity and can be used as general-purpose cells for clinical research, such as autoimmune diseases and graft-versus-host disease.

The invention discloses a medical application of DNA methyltransferase inhibitor combined with anti-CD47 antibody for preparing antineoplastic drugs, which will be appreciated by those skilled in theart, CD47 in physiological state can maintain the immune tolerance of the body's own cells, and in pathological state, it can be overexpressed in a variety of hematological tumors and solid tumors, through the combination of phagocyte ligands to initiate a series of inhibitory signal transduction to avoid phagocytosis, and inhibit the presentation of tumor antigens phagocytes, anti-CD47 antibody has anti-tumor effect. However, anti-CD47 antibodies alone are expensive and have limited efficacy. DNA methyltransferase inhibitors play an anti-tumor role by restoring the activity of tumor suppressor genes. As that DNA methyltransferase inhibitor and the anti-CD47 antibody combine to exhibit obvious synergistic effect on anti-tumor, the DNA methyltransferase inhibitor and the anti-CD47 antibodycan be combined to be use for anti-tumor, thereby enhancing the anti-tumor effect of the anti-CD47 antibody and reducing the economic burden of the patient.