生物活性

• 描述Mitoxantrone dihydrochloride is a potent topoisomerase II inhibitor. It is also showed inhibitory effect on protein kinase C (PKC) activity with IC50=8.5μM. Mitoxantrone inhibited PKC in a competitive manner with respect to histone H1 (Ki=6.3μM) and in a non-competitive manner with respect to phophatidylserine and ATP^[3]. Mitoxantrone dihydrochloride (0.5 μg/mL, 48 h) induces a decrease in B-CLL cells. Mitoxantrone dihydrochloride induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of Mitoxantrone dihydrochloride is due to induction of apoptosis^[4]. Mitoxantrone dihydrochloride (IP, 0-3.2 mg/kg/day) produces a statistically significant number of 60-day survivors at 1.6 mg/kg in mice with IP implanted L1210 leukemia. Mitoxantrone dihydrochloride (IV, 0-3.2 mg/kg/day) shows effective antitumor activities and produces a 60% ILS (increase in lifespan) at 3.2 mg/kg in SC implanted Lewis lung carcinoma^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A2780-cell	-	Growth inhibition assay	-	Concentration required to inhibit A2780-cell growth by 50%, IC50=0.55 nM	9703471
  A549 cells	-	Function assay	-	Activity against A549 cancer cell line, IC50=3.1 nM	8960558
  CCRF-CEM cells	-	Cytotoxicity assay	48 h	Cytotoxicity against human CCRF-CEM cells assessed as cell viability after 48 hrs by celltiter-blue assay, IC50=0.036 μM	22582991

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• 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
  NCT00004001	Prostate Cancer	Phase 3	Completed	-	United States, Arizona ... more >> CCOP - Scottsdale Oncology Program Scottsdale, Arizona, United States, 85259-5404 United States, Florida Mayo Clinic Jacksonville, Florida, United States, 32224 United States, Illinois CCOP - Illinois Oncology Research Association Peoria, Illinois, United States, 61602 CCOP - Carle Cancer Center Urbana, Illinois, United States, 61801 United States, Iowa CCOP - Cedar Rapids Oncology Project Cedar Rapids, Iowa, United States, 52403-1206 CCOP - Iowa Oncology Research Association Des Moines, Iowa, United States, 50309-1016 Siouxland Hematology-Oncology Sioux City, Iowa, United States, 51101-1733 United States, Minnesota Mayo Clinic Cancer Center Rochester, Minnesota, United States, 55905 CentraCare Health Plaza Saint Cloud, Minnesota, United States, 56303 United States, Nebraska CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska, United States, 68106 United States, North Dakota Medcenter One Health System Bismarck, North Dakota, United States, 58501 CCOP - Merit Care Hospital Fargo, North Dakota, United States, 58122 Altru Health System Grand Forks, North Dakota, United States, 58201 United States, Pennsylvania CCOP - Geisinger Clinic and Medical Center Danville, Pennsylvania, United States, 17822-2001 United States, South Dakota Rapid City Regional Hospital Rapid City, South Dakota, United States, 57709 CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota, United States, 57104 Collapse <<
  NCT00002498	Breast Cancer	Phase 2	Unknown	-	Netherlands ... more >> Leiden University Medical Center Leiden, Netherlands, 2300 ZA St. Radboud University Hospital Nijmegen, Netherlands, 6500 HB Collapse <<
  NCT00219908	Relapsing-Remitting Multiple S... more >>clerosis Collapse <<	Phase 2	Terminated	-	France ... more >> Hôpital Cote de Nacre Caen, France, 14033 Hôpital Gabriel Montpied Clermont-Ferrand, France, 63003 CHU Henri Mondor Creteil, France, 94000 Hôpital Général Dijon, France, 21033 CHU Limoges Limoges, France, 87042 Institut Catholique de Lille Lomme, France, 59462 Pierre Weitheimer Hospital Lyon, France, 69394 Chu Timone Marseille, France, 13385 Centre Guy de Chauliac Montpellier, France, 34295 CHU Hôpital Central Nancy, France, 54035 CHU Nice, France, 06000 CHU Pitié-Salpétrière Paris, France, 75013 Hôpital Saint-Anne Paris, France, 75014 Centre Fondation Rotschild Paris, France, 75019 Tenon Hospital Paris, France, 759170 CHU Strasbourg Strasbourg, France, 67000 CHU Purpan Toulouse, France, 31059 Italy Psichiatriche dell'Università di Bari, Policlinico Bari, Italy, 70122 Dipartimento di Scienze Neurologiche e Psichiatriche Firenze, Italy, 50134 Hospedal Civile Gallarate, Italy, 21013 Neuroriabilitazione dell'Università Genova, Italy, 16132 Fondazionz SAN Raffaele del monte tabor Milano, Italy, 20132 Clinica Neurologica Università di Torino Torino, Italy, 10126 Collapse <<

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• 参考文献

• [1] Seitz M. Molecular and cellular effects of methotrexate. Curr Opin Rheumatol. 1999 May;11(3):226-32.

  [2] Hirata S, Matsubara T, et al. Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate. Arthritis Rheum. 1989 Sep;32(9):1065-73.

  [3] Takeuchi N, Nakamura T, Takeuchi F, Hashimoto E, Yamamura H. Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. J Biochem. 1992;112(6):762-767.

  [4] Bellosillo B, Colomer D, Pons G, Gil J. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998;100(1):142-146. 

  [5] Fujimoto S, Ogawa M. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-162.

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