TUNEL labeling of free 3'-OH DNA ends demonstrated that cyclophosphamide promotes outer membrane blebbing, leading to DNA fragmentation, and promoting cleavage of the caspase 3 and caspase 7 substrate PARP in 9L/P450 cells. Bcl-2 expression totally prevents activation of initiator and effector caspase 3 in cells treated with activated cyclophosphamide. Bcl-2 suppresses the cytotoxic effects but not the cytostatic effects of activated cyclophosphamide [1]. Cyclophosphamide reversibly inhibits AChE with an IC50 of 511 μM [2]. Carbon tetrachloride does not impact the direct cytotoxicity of cyclophosphamide or 4-hydroxycyclophosphamide to cultivated cells [3].

Cyclophosphamide increases the percentage of cells stained for CD3, CD4, or CD8 in the spleen and tumors when given intraperitoneally (i.p.) to SW1 tumor-bearing C3H mice (2 mg/mouse in 0.1 mL PBS) [4].

Animal/Disease Models: Six- to eightweeks old female C3H/HeN mice bearing SW1 tumors [4]
Doses: 2 mg/mouse
Route of Administration: intraperitoneal (ip) injection; 2 mg/mouse in 0.1 mL PBS; Four-day
Experimental Results: spleen and an increase in the percentage of cells staining for CD3, CD4, or CD8 in the tumor.

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation Cyclophosphamide can appear in breast milk at concentrations that can reach toxic levels; furthermore, its highly toxic metabolites may increase the risk to the infant. Two cases of infants developing neutropenia have been reported, both in mothers who continued breastfeeding while receiving cyclophosphamide treatment. Most data suggest that breastfeeding should be avoided while the mother is receiving cytotoxic antitumor drugs, especially alkylating agents such as cyclophosphamide. Although some studies recommend suspending breastfeeding for 1 to 3 days after administration, the drug and its metabolites appear to take more than 21 days to be completely cleared from breast milk. Data from some authors indicate that after administration of 750 mg/m² cyclophosphamide, the drug concentration in breast milk may take up to 6 weeks to reach a safe level. Chemotherapy can adversely affect the normal microbiota and chemical composition of breast milk. Women receiving chemotherapy during pregnancy are more likely to experience breastfeeding difficulties.
◉ Effects on Breastfed Infants
A 23-day-old infant developed neutropenia, thrombocytopenia, and hypohemoglobinemia, possibly due to the mother receiving intravenous cyclophosphamide (6 mg/kg, total dose 300 mg) daily after 3 days of cyclophosphamide treatment.
A 4-month-old infant developed neutropenia, possibly due to the mother receiving cyclophosphamide (800 mg) intravenously once weekly, vincristine (2 mg), and prednisolone (30 mg) orally daily for 6 weeks after 9 days of cyclophosphamide treatment. Neutropenia persisted for at least 12 days and was accompanied by transient diarrhea.
A woman was diagnosed with B-cell lymphoma at 27 weeks of gestation. She was induced at 34 weeks and 4 days of gestation and began standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (dosage not specified), for 21 days, starting on day 2 postpartum. For the first 10 days of each treatment cycle, she expressed and discarded breast milk, feeding the baby with donated breast milk, and then breastfed for 10 days before the start of the next cycle. The 10-day breastfeeding pause was determined based on the half-life of vincristine (approximately 3 half-lives). After completing four cycles of chemotherapy, the baby was reported to be developing well without any complications.
◉ Effects on Lactation and Breast Milk
A case of normoprolactinemic galactorrhea was reported in a 55-year-old woman receiving cyclophosphamide treatment for pemphigus vulgaris. After one month of taking cyclophosphamide 50 mg/day, she developed bilateral breast engorgement and bilateral nipple discharge. No hormonal abnormalities were found. After discontinuing cyclophosphamide, her symptoms completely disappeared without recurrence. The galactorrhea was likely caused by cyclophosphamide.
A telephone follow-up study investigated 74 women who received cancer chemotherapy at the same center during mid- or late-pregnancy to determine their postpartum breastfeeding success rates. Only 34% of women were able to exclusively breastfeed their infants, and 66% reported breastfeeding difficulties. In contrast, the breastfeeding success rate was 91% among 22 mothers who were diagnosed during pregnancy but did not receive chemotherapy. Other statistically significant correlations included: 1. Mothers with breastfeeding difficulties received an average of 5.5 cycles of chemotherapy, while mothers without breastfeeding difficulties received an average of 3.8 cycles; 2. Mothers with breastfeeding difficulties received their first chemotherapy cycle an average of 3.4 weeks earlier. Among the 56 women treated with cyclophosphamide regimens, 34 experienced breastfeeding difficulties.

[1]. Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. Mol Pharmacol. 2001 Dec;60(6):1268-1279.

[2]. Administration of cyclophosphamide changes the immune profile of tumor-bearing mice. J Immunother. 2010 Jan;33(1):53-9.

[3]. Inhibition of human acetylcholinesterase by cyclophosphamide. Toxicology. 1995 Jan 19;96(1):1-6.

[4]. Carbon tetrachloride-induced increase in the antitumor activity of cyclophosphamide in mice: a pharmacokineticstudy. Cancer Chemother Pharmacol. 1984;12(3):167-72.

Cyclophosphamide monohydrate is a white, fine crystalline powder with a slightly bitter taste and almost no odor. (NTP, 1992)
Cyclophosphamide hydrate is the monohydrate of cyclophosphamide. It has antitumor, immunosuppressive, alkylating, and carcinogenic effects. It contains cyclophosphamide.
Cyclophosphamide is a synthetic alkylating agent whose chemical structure is related to nitrogen mustard drugs with antitumor and immunosuppressive activities. In the liver, cyclophosphamide is converted into the active metabolites aldehydephosphamide and phosphoramic acid mustard, which bind to DNA, thereby inhibiting DNA replication and initiating cell death.
Cyclophosphamide is a precursor to alkylated nitrogen mustard antitumor and immunosuppressant drugs and must be activated in the liver to form active aldehydephosphamide. It has been used to treat lymphoma and leukemia. Its side effect of hair loss was used to remove wool from sheep. Cyclophosphamide may also cause infertility, birth defects, gene mutations, and cancer.
See also: Cyclophosphamide (note moved to).

C7H17CL2N2O3P

279.1012

278.035

6055-19-2

Cyclophosphamide;50-18-0;Cyclophosphamide-d8 hydrate

22420

White to off-white solid powder

336.1ºC at 760 mmHg

49-51 °C(lit.)

>230 °F

2.148

2

5

5

15

212

0

PWOQRKCAHTVFLB-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O2P.H2O/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14;/h1-7H2,(H,10,12);1H2

N,N-bis(2-chloroethyl)-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine;hydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~179.15 mM)
DMSO : ≥ 38 mg/mL (~136.15 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 25 mg/mL (89.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)