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PR-104
PR-104 is a drug from the class of hypoxia-activated prodrugs (HAPs), which is being researched as a potential anti-cancer therapeutic agent. It is a phosphate ester “pre-prodrug” that is rapidly converted to the HAP PR-104A in the body. PR-104A is in turn metabolised to reactive nitrogen mustard DNA crosslinking agents in hypoxic tissues such as found in solid tumours. Following initial clinical studies, it was discovered that PR-104A is also activated by the enzyme AKR1C3 Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the ''AKR1C3'' gene. Function This gene encodes a member of t ..., independently of hypoxia. Hypoxia in the bone marrow of patients with leukaemia, and high activity of AKR1C3 in some leukaemia subtypes has led to interest in clinical trials of PR-104 in relapsed refractory acute leukaemias. References {{reflist Nitro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypoxia-activated Prodrugs
Hypoxia-Activated Prodrugs (HAPs) are prodrugs that target regions of tumor hypoxia within tumor cells. HAPs may offer the potential, alone and in combination with conventional chemotherapy, of improving cancer therapy. It is believed that tumor hypoxia contributes significantly to treatment failure and relapse among cancer patients because cells in the hypoxic zones of solid tumors resist traditional chemotherapy for at least two reasons: first, most antitumor agents cannot penetrate beyond 50-100 micrometers from capillaries, thereby never reaching those cells in the hypoxic regions. Secondly, the lower nutrient and oxygen supply to cells in the hypoxic zones of tumors cause them to divide more slowly than their well oxygenated counterparts, so hypoxic tumor cells exhibit greater resistance to chemotherapies and radiation which target rapidly dividing cells or require oxygen for efficacy. Hypoxia also contributes to the invasive and metastatic phenotypes of aggressive cancers by p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anti-cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of a cell. Ty ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nitrogen Mustard
Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents. Chemical warfare During World War II nitrogen mustards were studied at the Yale School of Medicine by Alfred Gilman and Louis Goodman, and classified human clinical trials of nitrogen mustards for the treatment of lymphoma started in December 1942. Also during World War II, an incident during the air raid on Bari, Italy, led to the release of mustard gas that affected several hundred soldiers and civilians. Medical examination of the survivors showed a decreased number of lymphocytes. After World War II was over, the Bari incident and the Yale group's studies eventually converged prompting a search for other similar compounds. Due to its use in previous studies, the nitrogen mustard known ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor Hypoxia
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior. Changes in the glycolytic pathway A particular change in metabolism, historically known as the Warburg effect results in high rates of glycolysis in both normoxic and hypoxic c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AKR1C3
Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is encoded by the ''AKR1C3'' gene. Function This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin D2, prostaglandin H2, and phenanthrenequinone, and the oxidation of prostaglandin F2α to prostaglandin D2. It is also capable of metabolizing estrogen and progesterone. AKR1C3 may play an important role in the development of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nitrogen Mustards
Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents. Chemical warfare During World War II nitrogen mustards were studied at the Yale School of Medicine by Alfred Gilman and Louis Goodman, and classified human clinical trials of nitrogen mustards for the treatment of lymphoma started in December 1942. Also during World War II, an incident during the air raid on Bari, Italy, led to the release of mustard gas that affected several hundred soldiers and civilians. Medical examination of the survivors showed a decreased number of lymphocytes. After World War II was over, the Bari incident and the Yale group's studies eventually converged prompting a search for other similar compounds. Due to its use in previous studies, the nitrogen mustard known ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Organophosphates
In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered as esters of phosphoric acid. Like most functional groups, organophosphates occur in a diverse range of forms, with important examples including key biomolecules such as DNA, RNA and ATP, as well as many insecticides, herbicides, nerve agents and flame retardants. OPEs have been widely used in various products as flame retardants, plasticizers, and performance additives to engine oil. The popularity of OPEs as flame retardants came as a substitution for the highly regulated brominated flame retardants. The low cost of production and compatibility to diverse polymers made OPEs to be widely used in industry including textile, furniture, electronics as plasticizers and flame retardants. These compounds are added to the final product physi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prodrugs
A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted (ADME). Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract. A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects. History Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone. For example, salicin is a β-D-glucopyranosid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sulfonates
In organosulfur chemistry, a sulfonate is a salt or ester of a sulfonic acid. It contains the functional group , where R is an organic group. Sulfonates are the conjugate bases of sulfonic acids. Sulfonates are generally stable in water, non-oxidizing, and colorless. Many useful compounds and even some biochemicals feature sulfonates. Sulfonate salts Anions with the general formula are called sulfonates. They are the conjugate bases of sulfonic acids with formula . As sulfonic acids tend to be strong acids, the corresponding sulfonates are weak bases. Due to the stability of sulfonate anions, the cations of sulfonate salts such as scandium triflate have application as Lewis acids. A classic preparation of sulfonates is the Strecker sulfite alkylation, in which an alkali sulfite salt displaces a halide, typically in the presence of an iodine catalyst: :RX + M2SO3 -> RSO3M + MX An alternative is the condensation of a sulfonyl halide with an alcohol in pyridine: :ROH + R' ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nitrobenzenes
Nitrobenzene is an organic compound with the chemical formula C6H5 NO2. It is a water-insoluble pale yellow oil with an almond-like odor. It freezes to give greenish-yellow crystals. It is produced on a large scale from benzene as a precursor to aniline. In the laboratory, it is occasionally used as a solvent, especially for electrophilic reagents. Production Nitrobenzene is prepared by nitration of benzene with a mixture of concentrated sulfuric acid, water, and nitric acid. This mixture is sometimes called "mixed acid." The production of nitrobenzene is one of the most dangerous processes conducted in the chemical industry because of the exothermicity of the reaction (Δ''H'' = −117 kJ/mol). World capacity for nitrobenzene in 1985 was about 1,700,000 tonnes. The nitration process involves formation of the nitronium ion (NO2+), followed by an electrophilic aromatic substitution reaction of it with benzene. The nitronium ion is generated by the reaction of nitric aci ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
