生物活性

• 描述The DNA alkylator is irreversibly crosslinked with DNA strand, which interferes with DNA synthesis. Ifosfamide is an alkylating chemotherapeutic agent that exhibits activity against a wide range of tumors^[3]. It was transformed into cytotoxic metabolites by enzymes in the liver. Ifosfamide is activated by the cytochrome P450 family. Ifosfamide inhibited the activity of CYP2B1 in C8III-1 cells at 0-5 mM. Only at high concentration (5 mM), Ifosfamide was cytotoxic to CrFK cells which did not express CYP2B1 ^[4]. The CYP-BM3 mutant activated ifosfamide, which inhibited U2OS cells^[5]. Ifosfamide administration prior to mating resulted in an increased percentage of post-implantation loss and resorbed fetuses in pregnant rats treated with 50 mg/kg ifosfamide at day 18 of gestation compared to the control rats. But Ifosfamide causes no obvious difference with the control rats at 25 mg/kg ^[3].
• 作用机制Ifosfamide is a DNA alkylator that exhibits activity against a wide range of tumors by being transformed into cytotoxic metabolites.
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00163761	Non-Hodgkin's Lymphoma ... more >> Hodgkin's Disease Collapse <<	Phase 2	Completed	-	Australia, Australian Capital ... more >>Territory Canberra Hospital Canberra, Australian Capital Territory, Australia, 2605 Australia, New South Wales Royal North Shore Hospital Sydney, New South Wales, Australia, 2065 Australia, Queensland Mater Adult Hospital South Brisbane, Queensland, Australia, 4101 Australia, Tasmania Royal Hobart Hospital Hobart, Tasmania, Australia, 7001 Australia, Victoria The Alfred Hospital Melbourne, Victoria, Australia, 3004 The Royal Melbourne Hospital Melbourne, Victoria, Australia, 3050 Frankston Hospital Melbourne, Victoria, Australia, 3199 Monash Medical Centre Melbourne, Victoria, Australia, 3199 Border Medical Oncology Wodonga, Victoria, Australia, 3690 Australia, Western Australia Fremantle Hospital Fremantle, Western Australia, Australia, 6160 Collapse <<
  NCT02441309	Osteosarcoma	Phase 2	Completed	-	Germany ... more >> Pediatric Hematology and Oncology, University Hospital Münster Münster, Germany, 48149 Italy Istituti Ortopedici Rizzoli Bologna, Emilia-Romagna, Italy, 40136 Netherlands Department of Clinical Oncology, Leiden University Medical Center Leiden, Postzone K1-P, Netherlands, P.O. Box 9600 Norway Radium Hospital, Oslo University Oslo, Norway, 0310 United Kingdom Leeds Teaching Hospitals NHS Trust Leeds, United Kingdom, LS9 7TF University College London Hospitals NHS Foundation Trust London, United Kingdom, NW1 2BU Christie Hospital NHS Foundation Trust Manchester, United Kingdom, M20 4BX Oxford University Hospitals NHS Foundations Trust Oxford, United Kingdom, OX3 7LE Collapse <<
  NCT01555710	Extensive-Stage Small Cell Lun... more >>g Cancer Collapse <<	Phase 3	Unknown	June 2015	-

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• 参考文献

• [1] Johnstone EC, Lind MJ, et al. Ifosfamide metabolism and DNA damage in tumour and peripheral blood lymphocytes of breast cancer patients. Cancer Chemother Pharmacol. 2000;46(6):433-41.

  [2] Chang TK, Yu L, et al. Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res. 1997 May 15;57(10):1946-54.

  [3] Helal M. Prenatal effects of transplacental exposure to ifosfamide in rats. Biotech Histochem. 2016 Jul;91(5):357-68

  [4] Karle P, Renner M, et al. Necrotic, rather than apoptotic, cell death caused by cytochrome P450-activated ifosfamide. Cancer Gene Ther. 2001 Mar;8(3):220-30

  [5] Vredenburg G, den Braver-Sewradj S, et al. Activation of the anticancer drugs cyclophosphamide and ifosfamide by cytochrome P450 BM3 mutants. Toxicol Lett. 2015 Jan 5;232(1):182-92

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