Cyclophosphamide
Cyclophosphamide, an inactive prodrug, is a kind of nitrogen mustard alkylating agent. Cyclophosphamide requires enzymatic and chemical activation. As a result, nitrogen mustard is produced. It causes DNA cross-linking that accounts for its cytotoxic properties. [1] IC50 of cytotoxicity in mouse embryo BALB/c 3T3 cells is 37.6 μM, [2] IC50 of cytotoxicity against human HL60 cells is 8.79 μM measured by MTT assay. [3]
Cyclophosphamide attaches the alkyl group to the guanine base of DNA causing its crosslinking, strand breakage and inducing mutations.
In vitro, cyclophosphamide has a dose-dependent, bimodal effect on the immune system. Low-dose cyclophosphamide not only decreases cell number but leads to decreased functionality of regulatory T cells (TREGs). Cyclophosphamide treatment enhances apoptosis and decreases homeostatic proliferation of these cells. Expression of GITR and FoxP3, which are involved in the suppressive activity of TREGs, is down-regulated after cyclophosphamide administration.[4] In primary human hepatocyte cultures, cyclophosphamide increases CYP3A4, CYP2C8, and CYP2C9 protein levels, causing its 4-hydroxylation rate enhance.[5] In somatic cells, cyclophosphamide produces gene mutations, chromosome aberrations, micronuclei and sister chromatid exchanges in a variety of cultured cells in the presence of metabolic activation as well as sister chromatid exchanges without metabolic activation. [6]
In vivo, it has produced chromosome damage and micronuclei in rats, mice and Chinese hamsters, and gene mutations in the mouse spot test and in the transgenic lacZ construct of Muta™Mouse. [6]
References:
[1] Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol. 2009 Nov; 6 (11):638-47.
[2] Moon KY, Kwon CH. N3-methyl-mafosfamide as a chemically stable, alternative prodrug of mafosfamide. Bioorg Med Chem Lett. 1998 Jul 7; 8 (13):1673-8.
[3] Patel MM, Mali MD, Patel SK. Bernthsen synthesis, antimicrobial activities and cytotoxicity of acridine derivatives. Bioorg Med Chem Lett. 2010 Nov 1; 20 (21):6324-6.
[4] Lutsiak ME, Semnani RT, De Pascalis R,et al. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood. 2005 Apr 1; 105 (7):2862-8. Epub 2004 Dec 9.
[5] Chang TK, Yu L, Maurel P, Waxman DJ. Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res. 1997 May 15; 57 (10):1946-54.
[6] Anderson D, Bishop JB, Garner RC, et al. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res. 1995 Aug; 330 (1-2):115-81.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 261.09 |
| Cas No. | 50-18-0 |
| Formula | C7H15Cl2N2O2P |
| Solubility | ≥11.85 mg/mL in H2O with gentle warming and ultrasonic; ≥13.05 mg/mL in DMSO; ≥50.8 mg/mL in EtOH |
| Chemical Name | N,N-bis(2-chloroethyl)-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine |
| SDF | Download SDF |
| Canonical SMILES | C1CNP(=O)(OC1)N(CCCl)CCCl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
9L gliosarcoma cells retrovirally transduced with CYP2B6 |
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Reaction Conditions |
1 mM cyclophosphamide for 48 h incubation |
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Applications |
Cyclophosphamide was shown to cause tumor cell death by stimulating apoptosis, as evidenced by the induction of plasma membrane blebbing, DNA fragmentation, and cleavage of the caspase 3 and caspase 7 substrate poly(ADP-ribose) polymerase in drug-treated cells. |
| Animal experiment:[2] | |
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Animal models |
Female C57BL/6 mice, 8 weeks of age |
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Dosage form |
2 mg Injected intraperitoneally |
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Applications |
Low-dose cyclophosphamide not only decreased the number of regulatory T cells (TREGs), but also led to decreased functionality of TREGs. Cyclophosphamide treatment enhanced apoptosis and decreased homeostatic proliferation of these cells. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Schwartz PS, Waxman DJ. Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. Molecular Pharmacology, 2001, 60(6): 1268-1279. 2. Lutsiak ME, Semnani RT, De Pascalis R, et al. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood, 2005, 105(7): 2862-2868. |
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Quality Control & MSDS
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Chemical structure
