生物活性

• 描述Dexrazoxane, a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid, is a cardioprotective agent. Dexrazoxane is well-tolerated, with myelosuppression being the dose-limiting toxicity in Phase I trials^[3]. As a single agent, dexrazoxane inhibited synchronized cultures of P. falciparum in human erythrocytes only at suprapharmacologic concentrations (> 200 microM). In combination with desferrioxamine B, dexrazoxane in pharmacologic concentrations (100-200 microM) moderately potentiated inhibition by approximately 20%. In contrast, pharmacologic concentrations of dexrazoxane (50-200 microM) as a single agent inhibited the progression of P. yoelli from sporozoites to schizonts in cultured mouse hepatocytes by 45 to 69%^[4]. Dexrazoxane preserved cardiac function without compromising EFS (event-free survival) and OS (overall survival) or increasing noncardiac toxicities^[5]. Dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade^[6]. Dexrazoxane may protect against RIHD (radiation-induced heart disease) by suppressing apoptosis and oxidative stress in cardiomyocytes^[7].
• 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
  NCT02786719	Neuroblastoma	Not Applicable	Recruiting	June 2019	United States, California ... more >> Rady Children's Hospital Recruiting San Diego, California, United States, 92123 Contact: Laura Conner    858-966-5983    LConner@rchsd.org    Principal Investigator: Peter Zage, MD          United States, Texas Texas Children's Hospital Recruiting Houston, Texas, United States, 77030 Contact: Sarah Whittle, MD, BA    832-822-4242    sbwhittl@txch.org Collapse <<
  NCT00077285	Sarcoma	Phase 2	Active, not recruiting	October 2019	United States, New York ... more >> Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10065 Collapse <<
  NCT00400946	Drug/Agent Toxicity by Tissue/... more >>Organ Leukemia Collapse <<	Phase 3	Active, not recruiting	June 2019	United States, Massachusetts ... more >> Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, New York Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx, New York, United States, 10461 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York, New York, United States, 10032 James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York, United States, 14642 United States, Rhode Island Hasbro Children's Hospital Providence, Rhode Island, United States, 02903 United States, Virginia INOVA Fairfax Hospital Fairfax, Virginia, United States, 22031 Canada, Ontario McMaster Children's Hospital at Hamilton Health Sciences Hamilton, Ontario, Canada, L8N 3Z5 Canada, Quebec Hopital Sainte Justine Montreal, Quebec, Canada, H3T 1C5 Centre de Recherche du Centre Hospitalier de l'Universite Laval Sainte Foy, Quebec, Canada, GIV 4G2 Puerto Rico San Jorge Children's Hospital Santurce, Puerto Rico, 00912 Collapse <<

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• 参考文献

• [1] Shaikh F, Dupuis LL, et al. Cardioprotection and Second Malignant Neoplasms Associated With Dexrazoxane in Children Receiving Anthracycline Chemotherapy: A Systematic Review and Meta-Analysis. J Natl Cancer Inst. 2015 Nov 23;108(4). pii: djv357.

  [2] Jones, R.L. Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity. Expert Rev Cardiovasc Ther, 2008. 6(10): p. 1311-7.

  [3] Jones RL. Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity. Expert Rev Cardiovasc Ther. 2008 Nov;6(10):1311-7

  [4] Loyevsky M, Sacci JB Jr, Boehme P, Weglicki W, John C, Gordeuk VR. Plasmodium falciparum and Plasmodium yoelii: effect of the iron chelation prodrug dexrazoxane on in vitro cultures. Exp Parasitol. 1999 Feb;91(2):105-14

  [5] Getz KD, Sung L, Alonzo TA, Leger KJ, Gerbing RB, Pollard JA, Cooper T, Kolb EA, Gamis AS, Ky B, Aplenc R. Effect of Dexrazoxane on Left Ventricular Systolic Function and Treatment Outcomes in Patients With Acute Myeloid Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 20;38(21):2398-2406

  [6] Yu X, Ruan Y, Shen T, Qiu Q, Yan M, Sun S, Dou L, Huang X, Wang Q, Zhang X, Man Y, Tang W, Jin Z, Li J. Dexrazoxane Protects Cardiomyocyte from Doxorubicin-Induced Apoptosis by Modulating miR-17-5p. Biomed Res Int. 2020 Mar 1;2020:5107193

  [7] Li L, Nie X, Zhang P, Huang Y, Ma L, Li F, Yi M, Qin W, Yuan X. Dexrazoxane ameliorates radiation-induced heart disease in a rat model. Aging (Albany NY). 2021 Jan 2;13(3):3699-3711

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