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| | Cyclophosphamide | | Systematic (IUPAC) name | | N,N-bis(2-chloroethyl)-2-oxo-1-oxa-3-aza -2u{5}-phosphacyclohexan-2-amine | | Identifiers | | CAS number | 50-18-0 | | ATC code | L01AA01 | | PubChem | 2907 | | DrugBank | APRD00408 | | Chemical data | | Formula | C7H15Cl2N2O2P | | Mol. mass | 261.085 g/mol | | SMILES | search in eMolecules, PubChem | | Physical data | | Melt. point | 2 °C (36 °F) | | Pharmacokinetic data | | Bioavailability | >75% (oral) | | Protein binding | >60% | | Metabolism | Hepatic | | Half life | 3-12 hours | | Excretion | Renal | | Therapeutic considerations | | Pregnancy cat. | D(AU) D(US) Image File history File links Cyclophosphamide structure. ...
Image File history File links Size of this preview: 669 × 600 pixelsFull resolution (1100 × 986 pixel, file size: 210 KB, MIME type: image/png) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Cyclophosphamide ...
IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ...
CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ...
The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ...
A section of the Anatomical Therapeutic Chemical Classification System. ...
PubChem is a database of chemical molecules. ...
The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ...
This article does not cite its references or sources. ...
General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ...
General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ...
General Name, Symbol, Number chlorine, Cl, 17 Chemical series halogens Group, Period, Block 17, 3, p Appearance yellowish green Standard atomic weight 35. ...
General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ...
General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ...
General Name, Symbol, Number phosphorus, P, 15 Chemical series nonmetals Group, Period, Block 15, 3, p Appearance waxy white/ red/ black/ colorless Standard atomic weight 30. ...
The molecular mass (abbreviated MM) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ...
BIC pen cap, about 1 gram. ...
The mole (symbol: mol) is the SI base unit that measures an amount of substance. ...
The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings. ...
The melting point of a crystalline solid is the temperature at which it changes state from solid to liquid. ...
In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ...
A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ...
Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ...
The liver is an organ present in vertebrates and some other animals. ...
It has been suggested that Effective half-life be merged into this article or section. ...
Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ...
It has been suggested that Renal anomalies and Renal plasma threshold be merged into this article or section. ...
The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
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| | Legal status | ℞ Prescription only The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
| | Routes | Oral, intravenous | Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ...
Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ...
The nitrogen mustards are cytotoxic chemotherapy agents similar to mustard gas. ...
Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. ...
Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...
A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ...
The liver is an organ present in vertebrates and some other animals. ...
Chemotherapy is the use of chemical substances to treat disease. ...
Uses
The main use of cyclophosphamide is together with other chemotherapy agents in the treatment of lymphomas, some forms of leukemia and some solid tumors. It is a chemotherapy drug that works by slowing or stopping cell growth. It also works by decreasing the immune system's response to various diseases. This article is about lymphoma in humans. ...
Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ...
In addition, its use is becoming more common in autoimmune diseases where disease-modifying antirheumatic drugs (DMARDs) have been ineffective. Systemic lupus erythematosus (SLE) with severe lupus nephritis, for example, may respond to pulsed cyclophosphamide. However in 2005, standard treatment for lupus nephritis changed to MMF from cyclophosphamide. Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ...
Disease-modifying antirheumatic drugs is a category of drugs used in many autoimmune diseases to slow down disease progression. ...
Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus (SLE), a disease of the immune system. ...
Mycophenolic acid (INN) (IPA: ) or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. ...
It is also used to treat Minimal Change Disease and rheumatoid arthritis. It is still used for Wegener's granulomatosis. The trade name is Endoxan. In medicine (rheumatology), Wegeners granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs. ...
Pharmacokinetics/Pharmacodynamics Cyclophosphamide is converted by mixed function oxidase enzymes in the liver to active metabolites. The main active metabolite is 4-hydroxycyclophosphamide. 4-hydroxycyclophosphamide exists in equilibrium with its tautomer, aldophosphamide. Most of the aldophosphamide is oxidised by the enzyme aldehyde dehydrogenase (ALDH) to make carboxyphosphamide. A small proportion of aldophosphamide is converted into phosphoramide mustard and acrolein. Acrolein is toxic to the bladder epithelium and can lead to hemorrhagic cystitis. This can be prevented through the use of aggressive hydration and/or Mesna. An oxidase is any enzyme that catalyzes an oxidation/reduction reaction involving molecular oxygen (O2) as the electron acceptor. ...
Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ...
Chemical equilibrium is the state in which the concentrations of the reactants and products have no net change over time. ...
Tautomers are organic compounds that are interconvertible by a chemical reaction called tautomerization. ...
Aldehyde Dehydrogenase Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation (dehydrogenation) of aldehydes. ...
In organic chemistry, acrolein or propenal is the simplest unsaturated aldehyde. ...
In anatomy, the urinary bladder is a hollow, muscular, and distensible (or elastic) organ that sits on the pelvic floor in mammals. ...
Types of epithelium This article discusses the epithelium as it relates to animal anatomy. ...
Hemorrhagic cystitis is diffuse inflammation of the bladder leading to hemorrhage. ...
Mesna (sodium 2-mercaptoethane sulfonate) is an adjuvant used in cancer chemotherapy involving cyclophosphamide and ifosfamide. ...
Recent clinical studies have shown that cyclophosphamide induce beneficial immunomodulatory effects in the context of adoptive immunotherapy. Although the mechanisms underlying these effects are not fully understood, several mechanisms have been suggested based on potential modulation of the host environment, including[citation needed]: An immunomodulator is a drug used for its effect on the immune system: drugs may be immunosuppressants or immunostimulators. ...
- Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
- Induction of T cell growth factors such as type I IFNs, and/or
- Enhanced grafting of adoptively transferred tumor-reactive effector T cells by the creation of an immunologic space niche.
Thus, cyclophosphamide pre-conditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens as well as active vaccination strategies, inducing objective anti-tumor immunity.
Mode of action The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells which have low levels of ALDH.
Phosphoramide mustard forms DNA crosslinks between (interstrand crosslinkages) and within (intrastrand crosslinkages) DNA strands at guanine N-7 positions. This leads to cell death.
Cyclophosphamide has relatively little typical chemotherapy toxicity as ALDHs are present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium. ALDHs protect these actively proliferating tissues against toxic effects phosphoramide mustard and acrolein by converting aldophosphamide to carboxyphosphamide that does not give rise to the toxic metabolites (phosphoramide mustard and acrolein). Sketch of bone marrow and its cells Pluripotential hemopoietic stem cells or pluripotential hematopoietic stem cells (PHSCs) are stem cells found in the bone marrow. ...
The liver is an organ present in vertebrates and some other animals. ...
In anatomy, the intestine is the portion of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine (or colon). ...
Types of epithelium This article discusses the epithelium as it relates to animal anatomy. ...
Side-effects Many people taking cyclophosphamide do not have serious side effects. Side-effects include chemotherapy-induced nausea and vomiting (CINV), bone marrow suppression, stomach ache, diarrhea, darkening of the skin/nails, alopecia (hair loss) and lethargy. Hemorrhagic cystitis is a frequent complication, but this is prevented by adequate fluid intake and Mesna (sodium 2-mercaptoethane sulfonate). Mesna is a sulfhydryl donor and binds acrolein. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...
Nausea and vomiting caused by chemotherapy; stomach upset may trigger a strong urge to vomit, or forcefully eliminate what is in the stomach. ...
Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. ...
Alopecia is a set of disorders ranging from male and female pattern alopecia (alopecia androgenetica), to alopecia areata, which involves the loss of some of the hair from the head, alopecia totalis, which involves the loss of all head hair, to the most extreme form, alopecia universalis, which involves the...
Fatigue is a feeling of excessive tiredness or lethargy, with a desire to rest, perhaps to sleep. ...
Hemorrhagic cystitis is diffuse inflammation of the bladder leading to hemorrhage. ...
Mesna (sodium 2-mercaptoethane sulfonate) is an adjuvant used in cancer chemotherapy involving cyclophosphamide and ifosfamide. ...
In organic chemistry, acrolein or propenal is the simplest unsaturated aldehyde. ...
Cyclophosphamide is itself carcinogenic, potentially causing transitional cell carcinoma of the bladder as a long-term complication. It can lower the body's ability to fight an infection. It can cause temporary or (rarely) permanent sterility. Although it is used to treat cancer, it may increase the risk of developing another form of cancer, sometimes months to years after treatment. The term carcinogen refers to any substance, radionuclide or radiation which is an agent directly involved in the promotion of cancer or in the facilitation of its propagation. ...
In medicine, carcinoma apanting dog named rufis It is malignant by definition: carcinomas invade surrounding tissues and organs, and may spread to lymph nodes and distal sites (metastasis). ...
Other (serious) side effects include:
- pink/bloody urine,
- unusual decrease in the amount of urine,
- mouth sores,
- unusual tiredness or weakness,
- joint pain,
- easy bruising/bleeding,
- stopping of menstrual periods,
- existing wounds that are slow healing.
History Cyclophosphamide and the related nitrogen mustard-derived alkylating agent ifosfamide were developed by Norbert Brock and ASTA (now Baxter Oncology). They converted the base nitrogen mustard into a non-toxic "transport form". This transport form was a pro-drug, subsequently actively transported into the cancer cells. Once in the cells, the pro-drug was enzymatically converted into the active, toxic form. Brock and his team synthesised more than 1,000 candidate oxazaphosphorine compounds, eventually finding the drug cyclophosphamide (Brock 1996). The nitrogen mustards are cytotoxic chemotherapy agents similar to mustard gas. ...
Ifosfamide (Mitoxana®) Ifosfamide (pronounced i fos fa mide) is chemotherapy that is given as a treatment for many different types of cancer. ...
Active transport is the mediated transport of biochemicals, and other atomic/molecular substances, across membranes. ...
Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ...
Reference - Brock N. The history of the oxazaphosphorine cytostatics. Cancer 1996;78:542-7. PMID 8697402.
External links - Links to external chemical sources
| Chemotherapeutic agents/Antineoplastic agents (L01) | | Alkylating agents | Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan). Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin). Platinum: (Carboplatin, Cisplatin, Oxaliplatin, BBR3464). Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, Uramustine | | Antimetabolites | Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine). Pyrimidine:(Capecitabine, Cytarabine, Fluorouracil, Floxuridine, Gemcitabine) | | Spindle poison plant alkaloids | Taxane: (Docetaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine). | | Cytotoxic/antitumor antibiotics | Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin). Bleomycin, Hydroxyurea, Mitomycin, Actinomycin | | Topoisomerase inhibitors | Camptotheca: (Camptothecin, Topotecan, Irinotecan), Podophyllum:(Etoposide, Teniposide). | | CI monoclonal antibodies | Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Tositumomab, Trastuzumab | | Photosensitizers | Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin | | Kinase inhibitors | Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib, Vandetanib (ZD6474) | | Other | Alitretinoin, Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase, Bexarotene, Bortezomib, Denileukin diftitox, Estramustine, Hydroxycarbamide, Masoprocol, Mitotane, Pegaspargase, Tretinoin | |
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