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Raltitrexed
Raltitrexed (Thaltitrexed, Tomudex, TDX, ZD 1694) is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca. Uses Used in treatment of colorectal cancer since 1998, it may also be used in the treatment of malignant mesothelioma. Raltitrexed is approved for use in Canada and some European countries, but is not approved by the US FDA. Mechanism of action Raltitrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites, which inhibit one or more of three enzymes that use folate and derivatives as substrates: DHFR, GARFT and thymidylate synthase. Raltitrexed is fully active after polyglutamylation, which allows cellular retention of the drug. By inhibiting Thymidylate synthase (TS), thus formation of precursor pyrimidine nucleotides, raltitrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal ce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antifolates
Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR). Comparison of available agents Image:Methotrexate skeletal.svg, Methotrexate Image:Pemetrexed.svg, Pemetrexed Image:Raltitrexed.svg, Raltitrexed Image:Pralatrexate.png, Pralatrexate Mechanism Many are primarily DHFR inhibitors, but raltitrexed is an inhibitor of thymidylate synthase, and pemetrexed inhibits both and a third enzyme. Antifolates act specifically du ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Intravenous Therapy
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water per os, by mouth. It may also be used to administer pharmaceutical drug, medications or other medical therapy such as blood transfusion, blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use. The intravenous route is the fastest way to deliver medications and fluid replacement throughout the body as they are introduced directly into the circulatory system and thus quickly distributed. For this reason, the intravenous route ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Polyglutamylation
Polyglutamylation is a form of reversible posttranslational modification of glutamate residues seen for example in alpha and beta tubulins, nucleosome assembly proteins NAP1 and NAP2. The γ-carboxy group of glutamate may form peptide-like bond with the amino group of a free glutamate whose α-carboxy group In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g. ... can now be extended into a polyglutamate chain. The glutamylation is done by the enzyme glutamylase and removed by deglutamylase. Polyglutamylation of chain length of up to six occurs in certain glutamate residues near the C terminus of most major forms of tubulins. These residues, though themselves not involved in direct binding, cause conformational shifts that regulate binding of microtubule associated proteins (MAP and Tau ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Quinazolinones
Quinazolinone is a heterocyclic chemical compound, a quinazoline with a carbonyl group in the C4N2 ring. Two isomers are possible: 2-quinazolinone and 4-quinazolinone, with the 4-isomer being the more common. These compounds are of interest in medicinal chemistry. File:2-Quinazolinone.png, 2-Quinazolinone File:4-Quinazolinone.png, 4-Quinazolinone Synthesis Common routes to quinazolines involve condensation of amides to anilines with ortho nitrile, carboxylic acids and amides. Derivatives Quinazolinone drugs that function as hypnotic/sedatives, methaqualone (Quaalude) for example, usually contain a 4-quinazolinone core with a 2-substituted phenyl group at nitrogen atom 3. See also * Idelalisib (Zydelig) * Cloroqualone * SL-164 (Dicloqualone) * Diproqualone * Etaqualone * Mebroqualone * Mecloqualone * Methylmethaqualone * Nitromethaqualone References {{Chemical classes of psychoactive drugs Quinazolinones, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drugs Developed By AstraZeneca
A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestion, absorption via a patch on the skin, suppository, or dissolution under the tongue. In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being. Traditionally drugs were obtained through extraction from medicinal plants, but more recently also by organic synthesis. Pharmaceutical drugs may be used for a limited duration, or on a regular basis for chronic disorders. Classification Pharmaceutical drugs are often classified into drug classes—groups of related drugs that have simila ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mammalian Dihydrofolate Reductase Inhibitors
A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles and birds, from which their ancestors diverged in the Carboniferous Period over 300 million years ago. Around 6,640 extant species of mammals have been described and divided into 27 orders. The study of mammals is called mammalogy. The largest orders of mammals, by number of species, are the rodents, bats, and eulipotyphlans (including hedgehogs, moles and shrews). The next three are the primates (including humans, monkeys and lemurs), the even-toed ungulates (including pigs, camels, and whales), and the Carnivora (including cats, dogs, and seals). Mammals are the only living members of Synapsida; this clade, together with Sauropsida (reptiles and birds), constitutes the lar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiophenes
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a planar five-membered ring, it is aromaticity, aromatic as indicated by its extensive substitution reactions. It is a colorless liquid with a benzene-like odor. In most of its reactions, it resembles benzene. Compounds analogous to thiophene include furan (C4H4O), selenophene (C4H4Se) and pyrrole (C4H4NH), which each vary by the heteroatom in the ring. Isolation and occurrence Thiophene was discovered by Viktor Meyer in 1882 as a contaminant in benzene. It was observed that isatin (an indole) forms a blue dye if it is mixed with sulfuric acid and crude benzene. The formation of the blue indophenin had long been believed to be a reaction of benzene itself. Viktor Meyer was able to isolate thiophene as the actual substance responsible for this reaction. Thiophene and especially its derivatives occur in petroleum, sometimes in concentrations up to 1–3%. The thiophenic content of Petroleum, oil and coal i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IC50
Half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, ''in vitro'', a given biological process or biological component by 50%. The biological component could be an enzyme, cell, cell receptor or microbe. IC50 values are typically expressed as molar concentration. IC50 is commonly used as a measure of antagonist drug potency in pharmacological research. IC50 is comparable to other measures of potency, such as EC50 for excitatory drugs. EC50 represents the dose or plasma concentration required for obtaining 50% of a maximum effect ''in vivo''. IC50 can be determined with functional assays or with competition binding assays. Sometimes, IC50 values are converted to the pIC50 scale. :\ce = -\log_ \ce Due to the minus sign, higher values of pIC50 indicate ex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
L1210
L1210 is a mouse lymphocytic leukemia cell line utilized in cancer research. L1210 cells are used to investigate new chemotherapeutic agents and as a model for observing drug resistance mechanisms in cancer treatment. These cells were originally derived from a mouse with Lymphoid leukemia, lymphocytic leukemia. History In 1954, Dr. Lloyd Law isolated the L1210 cell line by exposing DBA/2 mice to the chemical carcinogen 3-methylcholanthrene, 3-methylcholantrene. The cell line originated from the ascitic fluid of an 8-month-old female DBA/2 Inbred strain, strain mice with lymphoid leukemia. This was done by painting the skin with methylcholantrene, which induces tumors to allow researchers to study the process of cancer development. The L1210 cells were implanted Intraperitoneal injection, intraperitonealy (ip) through diluted ascitic fluid containing 105 L1210 cells per animal. The L1210 cells exhibited median death days ranging from 6.4 to 9.9 days and tumor doubling times rangin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thymidylate Synthase
Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage. Function The following reaction is catalyzed by thymidylate synthase: : 5,10-methylenetetrahydrofolate + dUMP \rightleftharpoons dihydrofolate + dTMP By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product. This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antimetabolite
An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used in chemotherapy for cancer. Function Cancer treatment Antimetabolites can be used in cancer treatment, as they interfere with DNA production and therefore cell division and tumor growth. Because cancer cells spend more time dividing than other cells, inhibiting cell division harms tumor cells more than other cells. Antimetabolite drugs are commonly used to treat leukemia, cancers of the breast, ovary, and the gastrointestinal tract, as well as other types of cancers. In the Anatomical Therapeutic Chemical Class ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
