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Antifolate
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 specificall ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Folic Acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an Nutrient#Essential nutrients, essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements. Folate in the form of folic acid is used to treat anemia caused by folic acid deficiency, folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby. NTDs include anencephaly and spina bifida, among other defects. Low levels in early pregna ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dihydrofolate Reductase
Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in one-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the ''DHFR'' gene. It is found in the q14.1 region of chromosome 5. There are two structural classes of DHFR, evolutionarily unrelated to each other. The former is usually just called DHFR and is found in bacterial chromosomes and animals. In bacteria, however, antibiotic pressure has caused this class to evolve different patterns of binding diaminoheterocyclic molecules, leading to many "types" named under this class, while mammalian ones remain highly similar. The latter (type II), represented by the plastid-encoded R67, is a tiny enzyme that works by forming a homotetramer. Function Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a proton shuttle required for the de no ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pralatrexate
Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Pralatrexate was approved for medical use in the United States in September 2009, as the first treatment for Peripheral T-cell Lymphoma (PTCL), an often aggressive type of non-Hodgkins lymphoma. Medical uses Pralatrexate is indicated for the treatment of people with relapsed or refractory peripheral T-cell lymphoma (PTCL). Mechanism Pralatrexate is a dihydrofolate reductase inhibitor. Discovery Research on this class of drugs began in the 1950s at SRI International, where scientists were focused on developing new chemotherapies and antifolates that would be effective against tumor cells A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persis ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyrimethamine
Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic diseases toxoplasmosis and cystoisosporiasis. It is also used with dapsone as a second-line option to prevent Pneumocystis pneumonia, ''Pneumocystis jiroveci'' pneumonia in people with HIV/AIDS. It was previously used for malaria but is no longer recommended due to resistance. Pyrimethamine is oral administration, taken by mouth. Common side effects include gastrointestinal upset, severe allergic reactions, and bone marrow suppression. It should not be used by people with folate deficiency that has resulted in anemia. There is concern that it may increase the risk of cancer. While occasionally used in pregnancy it is unclear if pyrimethamine is safe for the baby. Pyrimethamine is classified as a folic acid antagonist. It works by inhibiting f ... [...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] |
Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months of mild, flu-like illness such as muscle aches and tender lymph nodes. In a small number of people, eye problems may develop. In those with a Immunodeficiency, weakened immune system, severe symptoms such as seizures and poor coordination may occur. If a person becomes infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child. Toxoplasmosis is usually spread by eating poorly cooked food that contains Microbial cyst, cysts, by exposure to infected cat feces, or from an infected woman to her baby during pregnancy. Rarely, the disease may be spread by blood transfusion or other organ transplant. It is not otherwise spread between people. The parasite is only known to reproduce sexually in the Felidae, ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Methotrexate
Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given Oral administration, by mouth or by injection. Common side effects include nausea, feeling tired, fever, increased risk of infection, leukopenia, low white blood cell counts, and ulcerative stomatitis, breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pemetrexed
Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC). It is available as a generic medication. Medical use In February 2004, the U.S. Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the mesothelium, the thin layer of tissue that covers many of the internal organs, in combination with cisplatin for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology. Carboplatin Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer. However, the rel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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] |
Dihydrofolate Reductase 1DRF
Dihydrofolic acid (conjugate base dihydrofolate) (DHF) is a folic acid ( vitamin B9) derivative which is converted to tetrahydrofolic acid by dihydrofolate reductase. Since tetrahydrofolate is needed to make both purines and pyrimidines, which are building blocks of DNA and RNA, dihydrofolate reductase is targeted by various drugs to prevent nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ... synthesis. Interactive pathway map Further reading * References Folates {{organic-compound-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pneumocystis Pneumonia
''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus '' Pneumocystis jirovecii''. ''Pneumocystis'' specimens are commonly found in the lungs of healthy people although it is usually not a cause for disease. However, they are a source of opportunistic infection and can cause lung infections in people with a weak immune system or other predisposing health conditions. PCP is seen in people with HIV/AIDS (who account for 30-40% of PCP cases), those using medications that suppress the immune system, and people with cancer, autoimmune or inflammatory conditions, and chronic lung disease. Signs and symptoms Signs and symptoms may develop over several days or weeks and may include: shortness of breath and/or difficulty breathing (of gradual onset), fever, dry/non-productive cough, weight loss, night sweats, chills, and fatigue. Uncommonly, the infection may progress to involve other ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, Epileptic seizure, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected ''Anopheles'' mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial Immunity (medical), resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquitoes themselves are harmed by malaria, causing reduced lifespans in those infected by it. Malaria is caused by protozoa, single-celled microorganisms of the genus ''Plasmodium''. It is spread exclusively through bites of infected female ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
