Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.Fluorodeoxyuridylate: 5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.Deoxyuracil Nucleotides: Uracil nucleotides which contain deoxyribose as the sugar moiety.Thymidine Monophosphate: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.Folic Acid Antagonists: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.Antimetabolites, Antineoplastic: Antimetabolites that are useful in cancer chemotherapy.Dihydrouracil Dehydrogenase (NADP): An oxidoreductase involved in pyrimidine base degradation. It catalyzes the catabolism of THYMINE; URACIL and the chemotherapeutic drug, 5-FLUOROURACIL.ThiophenesTetrahydrofolates: Compounds based on 5,6,7,8-tetrahydrofolate.Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.QuinazolinesNucleoside-Phosphate Kinase: An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.Isoindoles: Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.Trimetrexate: A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.Folic Acid: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.Lactobacillus casei: A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina.Tetrahydrofolate Dehydrogenase: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.Pteroylpolyglutamic Acids: Derivatives of folic acid (pteroylglutamic acid). In gamma-glutamyl linkage they are found in many tissues. They are converted to folic acid by the action of pteroylpolyglutamate hydrolase or synthesized from folic acid by the action of folate polyglutamate synthetase. Synthetic pteroylpolyglutamic acids, which are in alpha-glutamyl linkage, are active in bacterial growth assays.Leukemia L1210Polyglutamic Acid: A peptide that is a homopolymer of glutamic acid.Methyltransferases: A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.Thymidine Phosphorylase: An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Thymine Nucleotides: Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)ThymidineLeucovorin: The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Glycine Hydroxymethyltransferase: A pyridoxal phosphate enzyme that catalyzes the reaction of glycine and 5,10-methylene-tetrahydrofolate to form serine. It also catalyzes the reaction of glycine with acetaldehyde to form L-threonine. EC 2.1.2.1.Hydroxymethyl and Formyl Transferases: Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.Orotate Phosphoribosyltransferase: The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10.Colonic Neoplasms: Tumors or cancer of the COLON.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Citrate (si)-Synthase: Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Glutamates: Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Reduced Folate Carrier Protein: A ubiquitously expressed folic acid transporter that functions via an antiporter mechanism which is coupled to the transport of organic phosphates.Kinetics: The rate dynamics in chemical or physical systems.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Lentinan: Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Guanine5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase: An enzyme that catalyzes the formation of methionine by transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine. It requires a cobamide coenzyme. The enzyme can act on mono- or triglutamate derivatives. EC 2.1.1.13.Phosphoribosylaminoimidazolecarboxamide Formyltransferase: An enzyme that catalyzes the conversion of aminoimidazole-4-carboxamide ribonucleotide to 5-formyl-aminoimidazole-4-carboxamide ribonucleotide in the purine de novo synthesis pathway. It requires the cofactor N(10)-FORMYLTETRAHYDROFOLATE as the formyl donor.Methylenetetrahydrofolate Reductase (NADPH2): A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11.Phosphoribosylglycinamide Formyltransferase: An enzyme that catalyzes the transfer of a formyl group from N10-formyltetrahydrofolate to N1-(5-phospho-D-ribosyl)glycinamide to yield N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide and tetrahydrofolate. It plays a role in the de novo purine biosynthetic pathway.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Nitric Oxide Synthase Type I: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.UracilMutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Flavins: Derivatives of the dimethylisoalloxazine (7,8-dimethylbenzo[g]pteridine-2,4(3H,10H)-dione) skeleton. Flavin derivatives serve an electron transfer function as ENZYME COFACTORS in FLAVOPROTEINS.Peptide Synthases: Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.Folate Receptors, GPI-Anchored: Cell surface receptors that bind to and transport FOLIC ACID, 5-methyltetrahydrofolate, and a variety of folic acid derivatives. The receptors are essential for normal NEURAL TUBE development and transport folic acid via receptor-mediated endocytosis.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.DCMP Deaminase: An enzyme that catalyzes the hydrolytic deamination of deoxycytidylic acid to deoxyuridylic acid and ammonia. It plays an important role in the regulation of the pool of deoxynucleotides in higher organisms. The enzyme also acts on some 5-substituted deoxycytidylic acids. EC 3.5.4.12.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Folate Receptor 1: A subtype of GPI-anchored folate receptors that is expressed in tissues of epithelial origin. This protein is also identified as an ovarian-tumor-specific antigen.Idoxuridine: An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.E2F1 Transcription Factor: An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.