| 名稱 | Ifosfamide |
| 描述 | Ifosfamide (NSC-109724) 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. |
| 激酶實驗 | 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. |
| 體外活性 | Ifosfamide誘導膀胱水腫,在Ifosfamide注射液后12小時達到峰值.顯微分析顯示血管充血、水腫、出血、纖維蛋白沉積、中性粒細胞浸潤和上皮剝蝕.誘導型一氧化氮合酶免疫反應在膀胱上皮細胞的細胞質中表現(xiàn)出強烈的反應性,可見彌漫性壞死.腹膜內注射給小鼠100 mg/kg,200 mg/kg和400 mg/kg Ifosfamide,依賴于劑量地誘導膀胱濕重和Evans藍外滲的增加.用mesna預處理可減少膀胱水腫的增加,而l - ng -硝基精氨酸甲酯、抗血清TNF-alpha或IL-1beta、thalidomide或pentoxifylline的治療可抑制膀胱水腫和顯微改變.抗血清治療也抑制了誘導型一氧化氮合酶在尿道上皮內的表達.誘導型一氧化氮合酶產生的一氧化氮參與了尿路上皮細胞的損傷,并參與了在小鼠的ifosfamide管理后導致出血性膀胱炎的炎癥反應. |
| 體內活性 | 在肝臟中,Ifosfamide它是一種由細胞色素P450混合功能氧化酶轉化為活性烷基化化合物的原藥物。在小兒實體瘤,卵巢癌,小細胞肺癌,非霍奇金和霍奇金淋巴瘤中,Ifosfamide均有良好的抗腫瘤效果。Ifosfamide（50 mM）使肝細胞中的CYP2C8/9,CYP3A4蛋白水平上升,進而使肝細胞自身的4-羥基化率提升。在CYP3A4表達量高于CYP3A5的肝細胞中,Ifosfamide僅誘導CYP3A4的表達。Ifosfamide對穩(wěn)定轉染CYP2B1的MCF-7細胞有較強細胞毒性（可被CYP2B1抑制劑美替拉酮顯著降低）,但不影響β-半乳糖苷酶表達和親本腫瘤細胞的MCF-7細胞。在預防腫瘤復發(fā)時,Ifosfamide和唑來膦酸聯(lián)用比單獨用藥,對骨形成的增加,組織修復的提高更有效。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : 48 mg/mL (183.8 mM)
DMSO : 55 mg/mL (210.66 mM)
Ethanol : 49 mg/mL (187.7 mM)
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| 關鍵字 | inhibit | DNA Alkylator/Crosslinker | NSC-109724 | Ifosfamide | Inhibitor | NSC 109724 |
| 相關產品 | N-Nitrosodiethylamine | Acyclovir | Guanidine hydrochloride | Trimethoprim | Procaine | Pemetrexed | Folic acid | Resveratrol | 5-Fluorouracil | Temozolomide | Thymidine | Ribavirin |
| 相關庫 | 抗癌活性化合物庫 | 抗癌上市藥物庫 | 經典已知活性庫 | FDA 上市藥物庫 | 藥物功能重定位化合物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 |