4-hydroperoxy Cyclophosphamide
(Synonyms: 培磷酰胺,4-OOH-CY) 目录号 : GC424014-hydroperoxy Cyclophosphamide（4-羟基过氧化环磷酰胺），环磷酰胺的活性代谢产物，能够交联DNA并独立于caspase受体激活诱导T细胞凋亡，通过产生活性氧（ROS）激活线粒体死亡途径。
Cas No.:39800-16-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | Primary human cytotoxic T cells (CTL) |
Preparation Method | Cell were cultured in the absence (untreated) or presence of 4-hydroperoxy Cyclophosphamide (3 μg/ml) for 48 h. |
Reaction Conditions | 3 μg/ml；48h |
Applications | 4-hydroperoxy Cyclophosphamide induces caspase-independent death of human cytotoxic T lymphocytes (CTL) after treatment. |
| Animal experiment [2]: | |
Animal models | BALB/c mice |
Preparation Method | Mice were injected i.p. with 200 mg/kg 4-hydroperoxy Cyclophosphamide. |
Dosage form | 200 mg/kg; i.p; 5days |
Applications | 4-hydroperoxy Cyclophosphamide treatment induces caspase-independent death in mouse T cells and B cells. |
References: [1]. Strauss G, Westhoff MA, et,al. 4-hydroperoxy-cyclophosphamide mediates caspase-independent T-cell apoptosis involving oxidative stress-induced nuclear relocation of mitochondrial apoptogenic factors AIF and EndoG. Cell Death Differ. 2008 Feb;15(2):332-43. doi: 10.1038/sj.cdd.4402272. Epub 2007 Nov 23. PMID: 18034189. | |
4-hydroperoxy Cyclophosphamide, the active metabolite of cyclophosphamide, can cross-link DNA and induce T cell apoptosis independently of caspase receptor activation. It also activates the mitochondrial death pathway through the production of reactive oxygen species (ROS). 4-hydroperoxy Cyclophosphamide is useful in research on rheumatoid arthritis and autoimmune diseases[1-2].
4-hydroperoxy Cyclophosphamide(1 μg/mL, 72-96 h), along with methotrexate, suppresses RANKL expression in IL-6/sIL-6R-stimulated fibroblast-like synoviocytes by inhibiting the JAK2/STAT3 and p38MAPK signaling pathways[3]. 4-hydroperoxy Cyclophosphamide (3 μg/ml; 48h) treatment resulted in the production of reactive oxygen species, increased levels of Bax, and the translocation of mitochondrial factors apoptosis-inducing factor (AIF) and endonuclease G (EndoG) to the nucleus. This treatment causes caspase-independent cell death in human CTL [4].
4-hydroperoxy Cyclophosphamide (200 mg/kg; i.p; 5 days) induced caspase-independent cell death in mouse T cells and B cells[4]. 4-hydroperoxy Cyclophosphamide (50-200 μg) intradermal injection at the sensitized site in guinea pig models of in-vivo contact sensitivity resulted in a significant enhancement of contact hypersensitivity [5].
References:
[1]. Fleer R, Brendel M. Toxicity, interstrand cross-links and DNA fragmentation induced by 'activated' cyclophosphamide in yeast: comparative studies on 4-hydroperoxy-cyclophosphamide, its monofunctional analogon, acrolein, phosphoramide mustard, and nor-nitrogen mustard. Chem Biol Interact. 1982 Mar 1;39(1):1-15. doi: 10.1016/0009-2797(82)90002-3. PMID: 7037214.
[2]. Chen Y, Ai L, et,al. The EZH2-H3K27me3 axis modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury. Cell Death Discov. 2023 Nov 14;9(1):413. doi: 10.1038/s41420-023-01705-6. PMID: 37963880; PMCID: PMC10646043.
[3]. Niu HQ, Zhao WP, et,al. Combination of 4-hydroperoxy cyclophosphamide and methotrexate inhibits IL-6/sIL-6R-induced RANKL expression in fibroblast-like synoviocytes via suppression of the JAK2/STAT3 and p38MAPK signaling pathway. Int Immunopharmacol. 2018 Aug;61:45-53. doi: 10.1016/j.intimp.2018.05.014. Epub 2018 May 24. PMID: 29803913.
[4]. Strauss G, Westhoff MA, et,al. 4-hydroperoxy-cyclophosphamide mediates caspase-independent T-cell apoptosis involving oxidative stress-induced nuclear relocation of mitochondrial apoptogenic factors AIF and EndoG. Cell Death Differ. 2008 Feb;15(2):332-43. doi: 10.1038/sj.cdd.4402272. Epub 2007 Nov 23. PMID: 18034189.
[5]. Boerrigter GH, de Groot J, et,al. Intradermal administration of 4-hydroperoxy-cyclophosphamide during contact sensitization potentiates effector T cell responsiveness in draining lymph nodes. Immunopharmacology. 1986 Feb;11(1):13-20. doi: 10.1016/0162-3109(86)90060-3. PMID: 3485619.
4-hydroperoxy Cyclophosphamide（4-羟基过氧化环磷酰胺），环磷酰胺的活性代谢产物，能够交联DNA并独立于caspase受体激活诱导T细胞凋亡，通过产生活性氧（ROS）激活线粒体死亡途径。4-hydroperoxy Cyclophosphamide在类风湿性关节炎和自身免疫疾病的研究中具有重要作用[1-2]。
4-hydroperoxy Cyclophosphamide(1 μg/mL, 72-96 h)与甲氨蝶呤联合使用，通过抑制JAK2/STAT3和p38MAPK信号通路，抑制IL-6/sIL-6R刺激下的类纤维母细胞突触细胞中的RANKL表达[3]。4-hydroperoxy Cyclophosphamide (3 μg/ml; 48h)处理导致活性氧（ROS）的产生，Bax水平的增加，以及线粒体因子凋亡诱导因子（AIF）和核酸酶G（EndoG）转移到细胞核。这种处理引起原代人细胞毒性T细胞(CTL)的caspase非依赖性细胞死亡[4]。
4-hydroperoxy Cyclophosphamide (200 mg/kg; i.p; 5 days)诱导了小鼠T细胞和B细胞的caspase非依赖性细胞死亡[4]。在豚鼠体内接触敏感性模型中，4-hydroperoxy Cyclophosphamide(50-200 μg)在敏感部位进行皮内注射，导致接触性过敏的显著增强[5]。
| Cas No. | 39800-16-3 | SDF | |
| 别名 | 培磷酰胺,4-OOH-CY | ||
| 化学名 | 2-[bis(2-chloroethyl)amino]tetrahydro-2-oxido-2H-1,3,2-oxazaphosphorin-4-yl, hydroperoxide | ||
| Canonical SMILES | O=P1(N(CCCl)CCCl)OCCC(OO)N1 | ||
| 分子式 | C7H15Cl2N2O4P | 分子量 | 293.1 |
| 溶解度 | DMSO : 50 mg/mL (170.60 mM; Need ultrasonic) | 储存条件 | -80°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4118 mL | 17.059 mL | 34.118 mL |
| 5 mM | 0.6824 mL | 3.4118 mL | 6.8236 mL |
| 10 mM | 0.3412 mL | 1.7059 mL | 3.4118 mL |
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动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Combination of 4-hydroperoxy Cyclophosphamide and methotrexate inhibits IL-6/sIL-6R-induced RANKL expression in fibroblast-like synoviocytes via suppression of the JAK2/STAT3 and p38MAPK signaling pathway
Int Immunopharmacol 2018 Aug;61:45-53.PMID:29803913DOI:10.1016/j.intimp.2018.05.014.
Although conventional combination therapy is effective for most patients with rheumatoid arthritis (RA), many still do not respond to current therapies. Therefore, novel combination regimens that better target cellular processes involved in RA pathogenesis are required. Preliminary studies have demonstrated the beneficial effects of a combination of cyclophosphamide (CTX) and methotrexate (MTX) in models of RA. Using western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and immunofluorescent staining, we demonstrated that the combination of 4-hydroperoxy CTX (4-H-CTX) and MTX inhibited the expression of receptor activator of nuclear factor-κB ligand (RANKL) in fibroblast-like synoviocytes (FLS) treated with the interleukin (IL)-6/soluble IL-6 receptor (sIL-6R) complex. To elucidate the mechanisms underlying this effect, we treated RA-FLS with the JAK2/STAT3 inhibitor AG490 or p38MAPK inhibitor SB203580. The results showed that IL-6/sIL-6R-induced RANKL upregulation required phosphorylation-mediated activation of STAT3 and p38 signaling, and that 4-H-CTX and/or MTX inhibited RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3 and p38MAPK signaling. This study demonstrated for the first time the inhibitory effects of 4-H-CTX and MTX on RANKL expression in IL-6/sIL-6R-stimulated FLS via suppression of STAT3 and p38MAPK phosphorylation. These results identify promising therapeutic agents that might have clinical applications in patients with RA who are at high risk of bone erosion or do not respond well to conventional therapy.
Ameliorative effect of recombinant human lactoferrin on the premature ovarian failure in rats after cyclophosphamide treatments
J Ovarian Res 2021 Jan 21;14(1):17.PMID:33478578DOI:10.1186/s13048-020-00763-z.
This study investigated the effect of recombinant human lactoferrin (rhLF) on the premature ovarian failure (POF) of rats. After cyclophosphamide treatments, the POF rats were divided into the following groups: normal control group (NC), low-dose group (LD), medium-dose group (MD) and high-dose group (HD) of rhLF. After drug administrations, the ovarian indexes and hormonal levels were detected. After follicle number count, the proliferation and apoptosis were analyzed with the expressions of genes related with oogenesis, reactive oxygen species (ROS) production and apoptosis detected, followed by the calculation of oxidative stress and protein expressions. After 4-hydroperoxy Cyclophosphamide (4-HC) treatments, the effect of rhLF on the proliferation, ROS production and gene expressions of primary rat granulosa cells (GCs) cultured in vitro were detected. After mating, the fertilities of POF rats were recorded. The result showed that the rhLF administrations up-regulated the ovarian index with the number of developing follicles increased and the decreases of hormonal levels conferred. The Ki-67 intensities of the MD and HD groups were up-regulated with the Tunnel intensities decreased. The rhLF treatments significantly promoted the expression of oogenesis, antioxidant and anti-apoptosis related genes. The expression of Bax and Caspase 3 were decreased with the expression of Bcl-2 up-regulated after rhLF administrations. The in vitro treatments of rhLF effectively conferred the toxicity of 4-HC on primary rat GCs. The fertility assessment showed the rhLF treatments up-regulated the offspring's' folliculogenesis, which confirmed the ameliorative role of rhLF on the POF damages via the inhibition of ROS production in GCs.