Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.
Antimetabolites that are useful in cancer chemotherapy.
Purines with a RIBOSE attached that can be phosphorylated to PURINE NUCLEOTIDES.
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.
An inhibitor of nucleotide metabolism.
Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety.
Any surgical procedure for treatment of glaucoma by means of puncture or reshaping of the trabecular meshwork. It includes goniotomy, trabeculectomy, and laser perforation.
The key substance in the biosynthesis of histidine, tryptophan, and purine and pyrimidine nucleotides.
An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 2.4.2.1.
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.
An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.
Leukemia L1210 is a designation for a specific murine (mouse) leukemia cell line that was originally isolated from a female mouse with an induced acute myeloid leukemia, which is widely used as a model in cancer research, particularly for in vivo studies of drug efficacy and resistance.
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.
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)
An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway.
Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Deoxycytidine is a nucleoside consisting of the pentose sugar deoxyribose linked to the nitrogenous base cytosine, which plays a crucial role in DNA replication and repair processes within cells.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
The rate dynamics in chemical or physical systems.
Pyrimidines with a RIBOSE and phosphate attached that can polymerize to form DNA and RNA.
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.
A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
Established cell cultures that have the potential to propagate indefinitely.
An enzyme, involved in the early steps of purine nucleotide biosynthesis, that catalyzes the formation of 5-phosphoribosylamine from glutamine and phosphoribosylpyrophosphate. EC 2.4.2.14.
Inborn errors of purine-pyrimidine metabolism refer to genetic disorders resulting from defects in the enzymes responsible for the metabolic breakdown and synthesis of purines and pyrimidines, leading to the accumulation of toxic metabolites or deficiency of necessary nucleotides, causing various clinical manifestations such as neurological impairment, kidney problems, and developmental delays.
Guanine is a purine nucleobase, one of the four nucleobases in the nucleic acid of DNA and RNA, involved in forming hydrogen bonds between complementary base pairs in double-stranded DNA molecules.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.
6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position.
Ribose substituted in the 1-, 3-, or 5-position by a phosphoric acid moiety.
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
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.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.
A purine base found in most body tissues and fluids, certain plants, and some urinary calculi. It is an intermediate in the degradation of adenosine monophosphate to uric acid, being formed by oxidation of hypoxanthine. The methylated xanthine compounds caffeine, theobromine, and theophylline and their derivatives are used in medicine for their bronchodilator effects. (Dorland, 28th ed)
An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. EC 2.4.2.7.
An enzyme that, in the course of purine ribonucleotide biosynthesis, catalyzes the conversion of 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole to 5'-phosphoribosyl-4-carboxamide-5-aminoimidazole and the conversion of adenylosuccinic acid to AMP. EC 4.3.2.2.
An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.
Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES.
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.
Proteins involved in the transport of nucleobases such as PYRIMIDINES and PURINES across membranes.
Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.
An enzyme that catalyzes the formation of phosphoribosyl pyrophosphate from ATP and ribose-5-phosphate. EC 2.7.6.1.
An inherited disorder transmitted as a sex-linked trait and caused by a deficiency of an enzyme of purine metabolism; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE. Affected individuals are normal in the first year of life and then develop psychomotor retardation, extrapyramidal movement disorders, progressive spasticity, and seizures. Self-destructive behaviors such as biting of fingers and lips are seen frequently. Intellectual impairment may also occur but is typically not severe. Elevation of uric acid in the serum leads to the development of renal calculi and gouty arthritis. (Menkes, Textbook of Child Neurology, 5th ed, pp127)
Purine bases found in body tissues and fluids and in some plants.
Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
Inosine nucleotides are purine nucleotides that contain inosine, a nucleoside with a hypoxanthine base, which can function as a weak agonist at adenosine receptors and play a role in the salvage pathways of nucleic acid metabolism.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
A carbon-nitrogen ligase. During purine ribonucleotide biosynthesis, this enzyme catalyzes the synthesis of adenylosuccinate from GTP; IMP; and aspartate with the formation of orthophosphate and GDP. EC 6.3.4.4.
Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent.
Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
A urea hydantoin that is found in URINE and PLANTS and is used in dermatological preparations.
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.
Pentosephosphates are monosaccharides, specifically pentoses, that have a phosphate group attached, playing crucial roles in carbohydrate metabolism, such as being intermediates in the pentose phosphate pathway and serving as precursors for nucleotide synthesis.
One of the early purine analogs showing antineoplastic activity. It functions as an antimetabolite and is easily incorporated into ribonucleic acids.
Pyrazolopyrimidine ribonucleosides isolated from Nocardia interforma. They are antineoplastic antibiotics with cytostatic properties.
Adenine nucleotides are molecules that consist of an adenine base attached to a ribose sugar and one, two, or three phosphate groups, including adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), which play crucial roles in energy transfer and signaling processes within cells.
Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
Proteins involved in the transport of NUCLEOSIDES across cellular membranes.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A purine or pyrimidine base bonded to DEOXYRIBOSE.