52 results about "Thymidylate synthase" patented technology

A Mob⁻ plasmid having a RSF1010 replicon, comprising a gene coding for Rep protein and said plasmid has been modified to inactivate gene related to mobilization ability. The present invention also describes a bacterium having an ability to produce useful metabolites, comprising the plasmid and said bacterium lack active thymidylate synthase coded by thyA gene and thymidine kinase coded by tdk gene, and a method for producing useful metabolites, such as native or recombinant proteins, enzymes, L-amino acids, nucleosides and nucleotides, vitamins, using the bacterium.

Novel DNA constructs and host cells comprising the same are disclosed. DNA constructs comprise a transcription unit (e.g. operon) comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin. In preferred embodiments, constructs further comprise DNA sequences encoding for thymidylate synthase and/or transcription units comprising sequences encoding for uridine kinase preferably together with dCTP deaminase. In particularly preferred embodiments, host cells comprising constructs having all of the above characteristics wherein the host cell displays repressed or no uracil DNA glycosylase activity. This may be achieved by removal of the host cell ung gene. Use of host cells in the manufacture of pyrimidine deoxyribonucleotides e.g. thymidine is also disclosed.

The invention discloses a preparation method of a biogas fermentation accelerant. The fermentation accelerant comprises trace metal elements such as Fe, Co, Ni and Zn. The preparation method comprise the following steps of preparing a thick salt solution in a chloride form; adding quantified thick salt solution into a fermenting methane pool every day, then stirring for well mixing the metal elements in fermentation liquor. The accelerant has good effect for biogas fermentation taking cow dung, pig manure and sheep manure as raw materials, and has good immediate effect on methanogens in biogas fermentation; if the accelerant is added in biogas fermentation, the methane yield can be improved and the methane content of the methane can be improved, the removal rate of COD (chemical oxygen demand), TS (thymidylate synthase) and VS can be obviously improved, and the accelerant has good prospect for promotion and application of the biogas fermentation.

The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.

Methods of treating cancer using antisense oligonucleotides directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense oligonucleotides can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

The protein EGFR, ERCC1, RRM1, thymidylate synthase, or beta-tubulin from cancer cells is detected in a blood sample by enriching the cancer cells from the blood sample followed by performing on the enriched cancer cells an immunoassay capable of detecting the proteins mentioned above. Cancer patients overexpressing EGFR are treated with an anti-EGFR agent, for example cetuximab, panitumumab, erlotinib or gefitinib.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM compounds”) which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.

The present invention relates to the use of genomic polymorphism to provide individualized therapeutic regimens to treat patients suffering from diseases such as cancer. The invention discloses methods for determining the efficacy or choice of chemotherapeutic drugs and regimens for use in treating a diseased patient by associating genomic polymorphism with the effectiveness of the drugs or regimens, or by associating genomic polymorphism with the intratumoral expression of a gene whereby the gene expression affects effectiveness of the drugs or regimens. In particular, the present invention provides novel methods for screening therapeutic regimens, which comprise determining a patient's genotype at a tandemly repeated 28 base pair region in the thymidilate synthase (TS) gene's 5′ untranslated region (UTR). Patients homozygous for a triple repeat will be least successfully treated with a thymidylate synthase directed drug, while those heterozygous for a triple and a double repeat will be more successfully treated, and those homozygous for a double repeat will be even more successfully treated. Those patients homozygous for the double repeat will likely suffer the least side effects from thymidylate synthase directed drugs such as 5-FU.

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyridyl-amino-pyrazine carbonitrile compounds that, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

Novel DNA constructs and host cells comprising the same are disclosed. DNA constructs comprise a transcription unit (e.g. operon) comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin or a uridine kinase gene and/or a dCTP deaminase gene. In preferred embodiments the constructs comprising DNA sequences encoding for ribonucleotide reductase and thioredoxin further comprise DNA sequences encoding for thymidylate synthase and/or transcription units comprising sequences encoding for uridine kinase preferably together with dCTP deaminase. In particularly preferred embodiments, the host cells comprise constructs having all of the above characteristics wherein the host cell displays repressed or no uracil DNA glycosylase activity. This may be achieved by removal of the host cell ung gene. Use of host cells in the manufacture of pyrimidine deoxyribonucleotides e.g. thymidine is also disclosed.

The invention discloses a kit and method for detecting the expression level of TYMS (Thymidylate Synthetase) mRNA (messenger Ribonucleic Acid). The kit comprises a standard substance and an internal reference gene real-time quantitative PCR (Polymerase Chain Reaction) system, wherein the standard substance is used for making a standard curve. Through the method, the expression level of TYMS can be accurately, rapidly and quantitatively determined. If the method and the kit, disclosed by the invention, are applied in clinic, doctors can rationally select fluorine drugs for treatment.

The present invention relates to a method for assessing the sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin and a method for selecting a patient for treatment of cancer with 10-propargyl-10-deazaaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer, wherein the polypeptide includes a member of folate pathways within cells and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT). The present invention also relates to the use of 10-propargyl-10-deazaaminopterin in the treatment of multiple myeloma.

The invention relates to a fluorescent quantitative PCR (polymerase chain reaction) kit for detecting human TYMS (thymidylate synthase) gene mutation. The kit mainly comprises specific primers and a PCR reaction reagent, wherein sequences of the specific primers are as follows: the sequence of an upstream primer is represented as 5'-ATCTTCCTCTGATGGCGCTG-3', and the sequence of a downstream primer is represented as 5'-AAAGGTCTGGGTTCTCGCTG-3'. The kit has the main benefits as follows: the kit is used for detecting the human TYMS gene expression quantity, is good in specificity and high in sensitivity and has the better application prospect.

The current invention is directed to a class of compounds that inhibit the function of Thymidylate synthase. Thymidylate synthase inhibition was noted to result in inhibition of tumor cell grow and killing of tumor cells. Thymidylate synthase inhibition is, thus, useful for treatment of various types of cancers, including but not limited to, acute lymphoblatic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute monocytic leukemia (AMOL), hairy cell leukemia, large cell immunoblastic lymphoma, plasmacytoma, multiple myeloma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, brain cancer, lung cancer, central nervous system (CNS) cancer, melanoma, renal cancer, prostate cancer, colon cancer, ovarian cancer and breast cancer. The compounds disclosed herein can be used alone or in combination with other cancer treatment regimens (e.g., radiation therapy and/or other chemotherapeutic agents that are administered to a subject having a tumor, cancer or neoplasia).

The objective of this invention is to create a double thyA folA knockout Escherichia coli (E. coli) strain for antifolate screening against DHFR of malaria and other parasites. This strain is used together with a plasmid expressing DHFR-TS from the desired pathogenic organism, which constitutes an anti-DHFR assay against the pathogenic organism of interest. The benefit of this invention is that there is no interference from either host DHFR or trimethoprim, a bacterial DHFR inhibitor. This tool is easy to use and maintain. It provides quick and reliable results as compared with conventional anti-malarial and anti-parasitic assays. This invention should facilitate discovery of new anti-DHFR compounds against malaria and other parasitic diseases.

The present invention provides antisense oligonucleotides useful for identifying drug targets for cancer therapies and for enhancing current cancer therapies. The oligonucleotides of the invention are complementary to thymidylate synthase mRNA and affect expression of at least one other gene. For the enhancement of cancer therapies, such antisense oligonucleotides can be used in conjunction with standard chemotherapeutic agents in order to target thymidylate synthase, as well as other appropriate targets. The antisense oligonucleotides and the methods of the invention constitute improved antisense therapies with application to a variety of cancers.

Novel thymidylate synthase (TS mutants) are disclosed differing from human wild type thymidylate synthase in single, double, or multiple mutations, which show intact enzyme activity and enhanced resistance to TS-inhibiting drugs like 5-fluorouracil or 5-fluoro-2-deoxyuridinemonophosphate. All these mutants can be used for the protection of normal human cell populations against the toxic manifestation of analogs that inhibited TS. Drugs for the local treatment or prevention of a mucositis in the oral cavity and the gastrointestinal tract caused by chemotherapy with TS-inhibitors are also provided.