Cyclophosphamide
(Synonyms: 环磷酰胺) 目录号 : GC11145
环磷酰胺是一种合成烷化剂，化学性质与氮芥有关，具有抗肿瘤活性，是一种免疫抑制剂。
Cas No.:50-18-0
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
Multiple Myeloma cell line (MM1.S) |
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Preparation Method |
MM1.S cells were treated with low dose concentrations of cyclophosphamide over a 48 hour time course, after which in vitro cell death was quantified by flow cytometry. |
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Reaction Conditions |
2.5, 5, 10, 20µM Cyclophosphamide for 48h. |
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Applications |
Low-dose cyclophosphamide treatment increased MM cell death in a dose-dependent manner, inducing moderate levels of cell death at 20µM cyclophosphamide after 24 hours and from 10µM cyclophosphamide after 48 hours. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
C57BL/6 mice were subcutaneously injected with B16F10 cells and daily treated in a low-dose Cyclophosphamide, Paclitaxel and Docetaxel Animals were monitored every 3 days for tumor growth. |
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Dosage form |
10 mg/kg Cyclophosphamide, intraperitoneal(i.p.) injection |
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Applications |
Cyclophosphamide chemotherapy significantly delays tumor growth as compared to the control group. At day 19, when all animals in both experimental groups were still alive and comparable, mice treated with metronomic chemotherapy showed a 70% reduction in tumor dimension.Such effect was directly correlated with reduction of CD4+ Tcells and parallel increase of CD8+ Tcells |
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References: [1]. Naicker SD, Feerick CL, et al. Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab through augmentation of macrophage-mediated antibody dependent cellular phagocytosis. Oncoimmunology. 2021 Jan 25;10(1):1859263. [2]. Tagliamonte M, Petrizzo A, et al. A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice. J Transl Med. 2016 Feb 24;14:58. |
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Cyclophosphamide is a frequently used chemotherapy, often in combination with other chemotherapy types, for the treatment of breast cancer, malignant lymphomas, multiple myeloma, and neuroblastoma[1].
Cyclophosphamide’s immunomodulatory function was investigated by conditioning macrophages with tumor cell secretome collected from cyclophosphamide treated MM cell lines. CTX-TCS conditioning augmented the migratory capacity of macrophages and increased CD32 and CD64 Fcγ receptor expression on their cell surface. Daratumumab-specific tumor clearance was increased by conditioning macrophages with CTX-TCS in a dose-dependent manner[2]
In vivo，Cyclophosphamide induces early nonapoptotic death of superficial cells, followed by apoptotic death of deeper layers. H&E staining was performed over several days to determine the global urothelial injury and regeneration pattern after cyclophosphamide injection. Compared with uninjured mice, significant sloughing of urothelial cell layers as well as submucosal hemorrhage and inflammation were observed 1 day after cyclophosphamide. cyclophosphamide induces nonapoptotic death of superficial cells starting at 2 hours, followed by apoptotic loss of intermediate and basal cells starting at 4 hours[3]
References:
[1]. Gernaat SAM, von Stedingk H, et al. Cyclophosphamide exposure assessed with the biomarker phosphoramide mustard-hemoglobin in breast cancer patients: The TailorDose I study. Sci Rep. 2021 Feb 1;11(1):2707.
[2]. Naicker SD, Feerick CL, et al. Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab through augmentation of macrophage-mediated antibody dependent cellular phagocytosis. Oncoimmunology. 2021 Jan 25;10(1):1859263.
[3]. Narla ST, Bushnell DS, et al. Keratinocyte Growth Factor Reduces Injury and Leads to Early Recovery from Cyclophosphamide Bladder Injury. Am J Pathol. 2020 Jan;190(1):108-124.
环磷酰胺是一种常用的化疗药物，通常与其他类型的化疗药物联合用于治疗乳腺癌、恶性淋巴瘤、多发性骨髓瘤和神经母细胞瘤[1]。
环磷酰胺的免疫调节功能是通过用从环磷酰胺处理的 MM 细胞系中收集的肿瘤细胞分泌蛋白组调节巨噬细胞来研究的。 CTX-TCS 调节增强了巨噬细胞的迁移能力并增加了其细胞表面的 CD32 和 CD64 Fcγ 受体表达。通过以剂量依赖性方式用 CTX-TCS 调节巨噬细胞，Daratumumab 特异性肿瘤清除率增加[2]
在体内，环磷酰胺诱导表层细胞的早期非凋亡性死亡，随后是深层细胞的凋亡性死亡。在几天内进行了 H&E 染色，以确定环磷酰胺注射后的整体尿路上皮损伤和再生模式。与未受伤的小鼠相比，在环磷酰胺给药1天后观察到尿路上皮细胞层明显脱落以及粘膜下出血和炎症。环磷酰胺从 2 小时开始诱导表层细胞的非凋亡性死亡，随后从 4 小时开始诱导中间细胞和基底细胞的凋亡性丢失[3]
| Cas No. | 50-18-0 | SDF | |
| 别名 | 环磷酰胺 | ||
| 化学名 | N,N-bis(2-chloroethyl)-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine | ||
| Canonical SMILES | C1CNP(=O)(OC1)N(CCCl)CCCl | ||
| 分子式 | C7H15Cl2N2O2P | 分子量 | 261.09 |
| 溶解度 | ≥ 13.05 mg/mL in DMSO, ≥ 11.85 mg/mL in Water with ultrasonic and warming, ≥ 50.8 mg/mL in EtOH | 储存条件 | 4°C, protect from light ,unstable in solution, ready to use. |
| 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 | 3.8301 mL | 19.1505 mL | 38.301 mL |
| 5 mM | 0.766 mL | 3.8301 mL | 7.6602 mL |
| 10 mM | 0.383 mL | 1.915 mL | 3.8301 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Cyclophosphamide and cancer: golden anniversary
Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.
Cyclophosphamide in dermatology
Cyclophosphamide is a chemotherapeutic agent which was first discovered in experimental tumours in rats, and it has since been widely used to treat malignancies and severe manifestations of various auto-immune diseases. High-dose chemotherapy and continuous daily oral regimens are associated with significant toxicity profiles, but i.v. pulsed regimens have lowered the rates of adverse effects in rheumatological studies. Cyclophosphamide has been shown to be useful in the treatment of severe autoimmune conditions due to its powerful immunosuppressive ability; however, it remains a relatively underused modality in dermatology. This article reviews the current literature on cyclophosphamide and its clinical applications in dermatology.
Mechanisms of Graft-versus-Host Disease Prevention by Post-transplantation Cyclophosphamide: An Evolving Understanding
Post-transplantation cyclophosphamide (PTCy) has been highly successful at preventing severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The clinical application of this approach was based on extensive studies in major histocompatibility complex (MHC)-matched murine skin allografting models, in which cyclophosphamide was believed to act via three main mechanisms: (1) selective elimination of alloreactive T cells; (2) intrathymic clonal deletion of alloreactive T-cell precursors; and (3) induction of suppressor T cells. In these models, cyclophosphamide was only effective in very specific contexts, requiring particular cell dose, cell source, PTCy dose, and recipient age. Achievement of transient mixed chimerism also was required. Furthermore, these studies showed differences in the impact of cyclophosphamide on transplanted cells (tumor) versus tissue (skin grafts), including the ability of cyclophosphamide to prevent rejection of the former but not the latter after MHC-mismatched transplants. Yet, clinically PTCy has demonstrated efficacy in MHC-matched or partially-MHC-mismatched HCT across a wide array of patients and HCT platforms. Importantly, clinically significant acute GVHD occurs frequently after PTCy, inconsistent with alloreactive T-cell elimination, whereas PTCy is most active against severe acute GVHD and chronic GVHD. These differences between murine skin allografting and clinical HCT suggest that the above-mentioned mechanisms may not be responsible for GVHD prevention by PTCy. Indeed, recent work by our group in murine HCT has shown that PTCy does not eliminate alloreactive T cells nor is the thymus necessary for PTCy's efficacy. Instead, other mechanisms appear to be playing important roles, including: (1) reduction of alloreactive CD4+ effector T-cell proliferation; (2) induced functional impairment of surviving alloreactive CD4+ and CD8+ effector T cells; and (3) preferential recovery of CD4+ regulatory T cells. Herein, we review the history of cyclophosphamide's use in preventing murine skin allograft rejection and our evolving new understanding of the mechanisms underlying its efficacy in preventing GVHD after HCT. Efforts are ongoing to more fully refine and elaborate this proposed new working model. The completion of this effort will provide critical insight relevant for the rational design of novel approaches to improve outcomes for PTCy-treated patients and for the induction of tolerance in other clinical contexts.