Cyclophosphamide structure
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Common Name | Cyclophosphamide | ||
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CAS Number | 50-18-0 | Molecular Weight | 261.086 | |
Density | 1.3±0.1 g/cm3 | Boiling Point | 336.1±52.0 °C at 760 mmHg | |
Molecular Formula | C7H15Cl2N2O2P | Melting Point | 41-45ºC | |
MSDS | N/A | Flash Point | 157.1±30.7 °C |
Use of CyclophosphamideCyclophosphamide is a synthetic alkylating agent chemically related to the nitrogen mustards with antineoplastic and immunosuppressive activities. |
Name | cyclophosphamide |
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Synonym | More Synonyms |
Description | Cyclophosphamide is a synthetic alkylating agent chemically related to the nitrogen mustards with antineoplastic and immunosuppressive activities. |
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Related Catalog | |
Target |
DNA Alkylator[1] |
In Vitro | Cyclophosphamide induces outer membrane blebbing, leads to DNA fragmentation, as revealed by TUNEL staining of free 3'-OH DNA ends, and induces cleavage of the caspase 3 and caspase 7 substrate PARP in 9L/P450 cells. Bcl-2 expression fully blocks the activation of both initiator caspases as well as the effector caspase 3 in cells treated with activated Cyclophosphamide. Bcl-2 inhibits the cytotoxic effects but not the cytostatic effects of activated Cyclophosphamide[1]. Cyclophosphamide inhibits the AChE reversibly with an IC50 of 511 μM[2]. Carbon tetrachloride does not affect the direct cytotoxicity of cyclophosphamide or 4-hydroxycyclophosphamide to cells in culture[3]. |
Kinase Assay | 9L cells are treated with drug for the times indicated in each experiment. Floating and attached cells are collected, pooled, resuspended in lysis buffer (10 mM HEPES buffer, pH 7.4, containing 2 mM EDTA, 0.1% CHAPS detergent, 5 mM DTT, 350 ng/mL phenylmethylsulfonyl fluoride, 10 ng/mL pepstatin A, 10 ng/mL aprotinin, and 20 ng/mL leupeptin) and lysed by three freeze-thaw cycles (alternating between a dry ice isopropanol bath and a 37°C water bath). Lysates are spun in a bench top centrifuge at full speed for 15 min and the supernatant (cell extract) fraction transferred to a new tube. Cell extracts (20 μL) are assayed for caspase 9, caspase 8, and caspase 3 activity by incubation at 37°C for either 1 h (caspase 3) or 3 h (caspase 9 and caspase 8) in 500 μL of reaction buffer (10 mM HEPES, pH 7.4, 2 mM EDTA, 0.1% CHAPS, and 5 mM DTT) containing 50 μM caspase form-selective substrate: Ac-LETD-AFC for caspase 8; Ac-LEHD-AFC for caspase 9; and Ac-DEVD-AMC for caspase 3. Background activity is determined for each sample as follows. Cell extracts are preincubated for 15 min at room temperature, with or without caspase form-selective inhibitor: 1 μM z-LETD-FMK for caspase 8, 1 μM z-LEHD-FMK for caspase 9, and 5 μL of Casputin for caspase 3. Caspase activity measured in the absence of inhibitor is divided by the background caspase activity measured in the presence of inhibitor. A value of 1 is subtracted from each measured activity, such that a caspase activity of 0 corresponds to no increase in the specific caspase activity with drug treatment. Fluorescence of the caspase product (excitation at 395 nm and emission at 525 nm for AFC substrates, and excitation at 380 nm and emission at 460 nm for the AMC substrate) is measured using a Shimadzu model RF-1501 spectrofluorophotometer and the manufacturer's PC-1501 software package. |
Cell Assay | 9L/pBabe, 9L/Bax, and 9L/Bcl-2 cells are treated with 12, 24, or 50 μM MFA for 72 h. Cells remaining on the plates at 0, 24, 48, and 72 h are washed twice with cold PBS and then stained for 5 min with crystal violet [1.25 g of crystal violet dissolved in a solution containing 50 mL of 37% formaldehyde and 450 mL of methanol]. The stained cells are washed three times in tap water and the plates are allowed to dry. The stain is eluted from the cells with 70% ethanol and the absorbance is then read at 595 nm. The staining intensity of each drug-treated sample (A 595) is then graphed as a percentage of the staining intensity at the 0-h time point. |
References |
Density | 1.3±0.1 g/cm3 |
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Boiling Point | 336.1±52.0 °C at 760 mmHg |
Melting Point | 41-45ºC |
Molecular Formula | C7H15Cl2N2O2P |
Molecular Weight | 261.086 |
Flash Point | 157.1±30.7 °C |
Exact Mass | 260.024811 |
PSA | 51.38000 |
LogP | 0.23 |
Vapour Pressure | 0.0±0.7 mmHg at 25°C |
Index of Refraction | 1.506 |
Stability | Stable, but light sensitive. Incompatible with oxidizing agents. |
Water Solubility | Soluble. 1-5 g/100 mL at 23 ºC |
Synonym:N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate; 2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazophosphorine 2-oxide monohydrate; Cancer research tool Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
Risk Phrases: 25 41 45 46 48/23/24/25 61 Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW
Toxic if swallowed. Risk of serious damage to eyes. May cause cancer. May cause heritable genetic damage. Toxic : danger of serious damage to health by prolonged exposure through inhalation, contact with skin and if swallowed. May cause harm to the unborn child. Potential Health Effects Eye: Causes severe eye irritation and possible injury. Skin: May cause skin irritation. May be harmful if absorbed through the skin. Ingestion: May cause irritation of the digestive tract. Poison by ingestion. May cause nausea and vomiting. Inhalation: May cause respiratory tract irritation. May be harmful if inhaled. May cause nausea and possible vomiting. Chronic: May cause cancer in humans. May cause reproductive and fetal effects. Section 4 - FIRST AID MEASURES Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately. Skin: Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Ingestion: Get medical aid immediately. Wash mouth out with water. Inhalation: Get medical aid immediately. Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Notes to Physician: Treat symptomatically and supportively. Section 5 - FIRE FIGHTING MEASURES General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. Will burn if involved in a fire. This material in sufficient quantity and reduced particle size is capable of creating a dust explosion. Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. Section 6 - ACCIDENTAL RELEASE MEASURES General Information: Use proper personal protective equipment as indicated in Section 8. Spills/Leaks: Vacuum or sweep up material and place into a suitable disposal container. Avoid generating dusty conditions. Provide ventilation. Section 7 - HANDLING and STORAGE Handling: Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Minimize dust generation and accumulation. Do not get in eyes, on skin, or on clothing. Take precautionary measures against static discharges. Do not breathe dust. Use only with adequate ventilation. Storage: Store in a cool, dry place. Store in a tightly closed container. Keep under an argon blanket. Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 50-18-0: CAS# 6055-19-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166. Skin: Wear appropriate protective gloves to prevent skin exposure. Clothing: Wear appropriate protective clothing to prevent skin exposure. Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Solid Color: white to almost white Odor: odorless pH: 4 - 6 (2% aq soln) Vapor Pressure: 0.000033 HPa @ 20 deg C Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 49 - 53 deg C Autoignition Temperature: Not available. Flash Point: > 112 deg C (> 233.60 deg F) Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: 90 deg C Solubility in water: 40 g/l water Specific Gravity/Density: Molecular Formula: C7H15Cl2N2O2P.H2O Molecular Weight: 279.09 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Stable at room temperature in closed containers under normal storage and handling conditions. Exothermic decomposition at 90C (Method VDI 2263). Conditions to Avoid: Dust generation, excess heat. Incompatibilities with Other Materials: Strong oxidizing agents, acids, bases. Hazardous Decomposition Products: Hydrogen chloride, nitrogen oxides, phosphine, carbon monoxide, oxides of phosphorus, carbon dioxide. Hazardous Polymerization: Has not been reported. Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 50-18-0: RP5950000 CAS# 6055-19-2: RP6157750 LD50/LC50: CAS# 50-18-0: Oral, mouse: LD50 = 137 mg/kg; Oral, rat: LD50 = 100 mg/kg. CAS# 6055-19-2: Oral, mouse: LD50 = 350 mg/kg; Oral, rat: LD50 = 94 mg/kg. Primary irritative effect to the eyes: Corrosive, rabbit, OECD 405. Carcinogenicity: Cyclophosphamide (anhydrous form) - California: carcinogen, initial date 2/27/87 NTP: Known carcinogen IARC: Group 1 carcinogen Cyclophosphamide monohydrate - California: carcinogen, initial date 2/27/87 IARC: Group 1 carcinogen Other: See actual entry in RTECS for complete information. Section 12 - ECOLOGICAL INFORMATION Other No information available. Section 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations. Section 14 - TRANSPORT INFORMATION IATA Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.* Hazard Class: 6.1 UN Number: 2811 Packing Group: III IMO Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing Group: III RID/ADR Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing group: III USA RQ: CAS# 50-18-0: 10 lb final RQ; 4.54 kg final RQ Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: T Risk Phrases: R 45 May cause cancer. R 46 May cause heritable genetic damage. R 61 May cause harm to the unborn child. R 25 Toxic if swallowed. R 41 Risk of serious damage to eyes. R 48/23/24/25 Toxic : danger of serious damage to health by prolonged exposure through inhalation, contact with skin and if swallowed. Safety Phrases: S 53 Avoid exposure - obtain special instructions before use. S 15 Keep away from heat. S 26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible). WGK (Water Danger/Protection) CAS# 50-18-0: No information available. CAS# 6055-19-2: 3 Canada CAS# 50-18-0 is listed on Canada's DSL List. CAS# 50-18-0 is not listed on Canada's Ingredient Disclosure List. CAS# 6055-19-2 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 50-18-0 is not listed on the TSCA inventory. It is for research and development use only. CAS# 6055-19-2 is not listed on the TSCA inventory. It is for research and development use only. SECTION 16 - ADDITIONAL INFORMATION N/A |
Safety Phrases | S22-S24/25 |
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RIDADR | UN 1851 |
Packaging Group | III |
Hazard Class | 6.1(b) |
HS Code | 2924299090 |
~% Cyclophosphamide CAS#:50-18-0 |
Literature: Angewandte Chemie, , vol. 70, p. 539,543 |
~% Cyclophosphamide CAS#:50-18-0 |
Literature: Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, , vol. 52, # 8 p. 943 - 946 |
~78% Cyclophosphamide CAS#:50-18-0 |
Literature: US2014/66654 A1, ; Paragraph 0039; 0040; 0041; 0042 ; |
~0% Cyclophosphamide CAS#:50-18-0 |
Literature: Journal of Medicinal Chemistry, , vol. 24, # 12 p. 1404 - 1408 |
Precursor 4 | |
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DownStream 10 | |
HS Code | 2934999090 |
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Summary | 2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |
ASTA |
N,N-Bis(b-chloroethyl)-N',O-propylenephosphoric Acid Ester Diamide |
cycloblastin |
cyclophosphane |
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide |
2H-1,3,2-Oxazaphosphorine, 2-(bis(2-chloroethyl)amino)tetrahydro-, 2-oxide |
N,N-bis(2-chloroéthyl)-1,3,2-oxazaphosphinan-2-amine-2-oxyde |
2-(Bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazophosphorine 2-oxide |
Mitoxan |
cytophosphan |
B 518 |
2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide |
EINECS 200-015-4 |
N,N-Bis(b-chloroethyl)-N',O-trimethylenephosphoric Acid Ester Diamide |
CB 4564 |
2-(bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide |
Clafen |
Cytoxan |
Endoxana |
N,N-Bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide |
Endoxan |
UNII:6UXW23996M |
Enduxan |
2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide |
Neosar |
Genoxal |
Cyclophosphamide |
2-[Bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazophosphorine 2-Oxide |
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide |
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide (9CI) |
(RS)-Cyclophosphamide |
Ciclophosphamide |
(±)-Cyclophosphamide |
2-(bis(2-Chloroethyl)-amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide |