Ifosfamide 是一种烷化剂，具有抗肿瘤活性。它烷基化并形成 DNA 交联，从而防止 DNA 链分离和 DNA 复制。它是一种前药，必须通过肝微粒体酶的羟基化来激活。
产品描述
Ifosfamide alkylates and forms DNA crosslinks, thereby preventing DNA strand separation and DNA replication. Ifosfamide is a synthetic analog of the nitrogen mustard cyclophosphamide with antineoplastic activity. This agent is a prodrug that must be activated through hydroxylation by hepatic microsomal enzymes.
体外活性
Ifosfamide诱导膀胱水肿,在Ifosfamide注射液后12小时达到峰值.显微分析显示血管充血、水肿、出血、纤维蛋白沉积、中性粒细胞浸润和上皮剥蚀.诱导型一氧化氮合酶免疫反应在膀胱上皮细胞的细胞质中表现出强烈的反应性,可见弥漫性坏死.腹膜内注射给小鼠100 mg/kg,200 mg/kg和400 mg/kg Ifosfamide,依赖于剂量地诱导膀胱湿重和Evans蓝外渗的增加.用mesna预处理可减少膀胱水肿的增加,而l - ng -硝基精氨酸甲酯、抗血清TNF-alpha或IL-1beta、thalidomide或pentoxifylline的治疗可抑制膀胱水肿和显微改变.抗血清治疗也抑制了诱导型一氧化氮合酶在尿道上皮内的表达.诱导型一氧化氮合酶产生的一氧化氮参与了尿路上皮细胞的损伤,并参与了在小鼠的ifosfamide管理后导致出血性膀胱炎的炎症反应.
体内活性
在肝脏中,Ifosfamide它是一种由细胞色素P450混合功能氧化酶转化为活性烷基化化合物的原药物。在小儿实体瘤,卵巢癌,小细胞肺癌,非霍奇金和霍奇金淋巴瘤中,Ifosfamide均有良好的抗肿瘤效果。Ifosfamide（50 mM）使肝细胞中的CYP2C8/9,CYP3A4蛋白水平上升,进而使肝细胞自身的4-羟基化率提升。在CYP3A4表达量高于CYP3A5的肝细胞中,Ifosfamide仅诱导CYP3A4的表达。Ifosfamide对稳定转染CYP2B1的MCF-7细胞有较强细胞毒性（可被CYP2B1抑制剂美替拉酮显著降低）,但不影响β-半乳糖苷酶表达和亲本肿瘤细胞的MCF-7细胞。在预防肿瘤复发时,Ifosfamide和唑来膦酸联用比单独用药,对骨形成的增加,组织修复的提高更有效。
激酶实验
cAMP kinase assay: Diced epididymal fat pads from fed Wistar rats (175-225 gm) are obtained after decapitation and incubated at 37 °C for two hours in Krebs-bicarbonate buffer containing 1.27 mM CaCl2. When added, Tolbutamide is present only during the incubation. After incubation fat pads are rinsed and sonicated in cold Krebs-bicarbonate buffer. The aqueous supematants from centrifugation at 50,000 × g for 30 minutes at 4 °C contained 0.75 to 1.25 mg protein per mL and are assayed for cyclic AMP-stimulated protein kinase activity. The assay is performed in 0.2 mL with these additions, 10 μmoles sodium glycerofiosphate pH 7.0, 2 μmoles sodium fluoride, 0.4 μmoles theophylline, 0.1 μmoles ethylene glyool bis (β-aminoethyl ether)-N, N'-tetraaoetic acid, 3 μmoles magnesium chloride, 0.3 mg mixed histone, 2 nmoles (γ- 32P) ATP, 1 nmoles cyclic AMP when indicated, and 0.05 ml of supernatant.
Cas No.
3778-73-2
分子式
C7H15Cl2N2O2P
分子量
261.09
别名
Isophosphamide;NSC109724;异环磷酰胺
储存和溶解度
H2O:48 mg/mL (183.8 mM)
DMSO:49 mg/mL (187.7 mM)
Ethanol:49 mg/mL (187.7 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years
