Medical University of Lodz, Department of Hematology, Lodz, Poland.
Expert Opin Investig Drugs. 2011 Mar;20(3):343-59. doi: 10.1517/13543784.2011.554822.
In the last few years, several new purine and pyrimidine nucleoside analogs have been synthesized and made available for both preclinical studies and clinical trials.
This article summarizes recent achievements in the mechanism of action, pharmacological properties and clinical activity and toxicity as well as the emerging role of newer purine and pyrimidine nucleoside analogs potentially active in lymphoid and myeloid malignancies. A literature review was conducted from the MEDLINE database PubMed for articles in English. Publications from 2000 to October 2010 were scrutinized. The search terms used were clofarabine, nelarabine, forodesine, 8-chloroadenosine, LMP-420, azacitidine, decitabine, sapacitabine, troxacitabine, thiarabine and zebularine in conjunction with hematologic malignancies, leukemia and lymphoma. Conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, and American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.
Several new nucleoside analogs are currently under investigation in preclinical and clinical studies concerning hematological malignancies. Clofarabine, nelarabine, azacitidine and decitabine have been recently approved for the treatment of leukemias and/or myelodysplastic syndromes. Other agents including forodesine, 8-chloroadenosine, LMP-420, sapacitabine, troxacitabine, thiarabine and zebularine seem to be promising for the treatment of lymphoid and myeloid malignancies. However, definitive data from ongoing and future clinical trials will aid in better defining their status in the treatment of hematological disorders.
在过去的几年中，已经合成了几种新的嘌呤和嘧啶核苷类似物，并可用于临床前研究和临床试验。
本文总结了最近在作用机制、药理学特性和临床活性和毒性方面的成就，以及在潜在治疗淋巴和骨髓恶性肿瘤方面具有活性的新型嘌呤和嘧啶核苷类似物的新兴作用。从 MEDLINE 数据库 PubMed 中以英文发表的文章进行了文献回顾。审查了 2000 年至 2010 年 10 月的出版物。使用的搜索词是氯法拉滨、奈拉滨、氟达拉滨、8-氯腺苷、LMP-420、阿扎胞苷、地西他滨、 sapacitabine、troxacitabine、硫鸟嘌呤和 zebularine 与血液恶性肿瘤、白血病和淋巴瘤。手动搜索了过去 5 年美国血液学会、欧洲血液学协会和美国临床肿瘤学会的会议记录。通过查看所选文章的参考文献获得了其他相关出版物。
目前正在进行涉及血液系统恶性肿瘤的临床前和临床研究，以评估几种新的核苷类似物。氯法拉滨、奈拉滨、阿扎胞苷和地西他滨已被批准用于治疗白血病和/或骨髓增生异常综合征。其他药物，包括氟达拉滨、8-氯腺苷、LMP-420、sapacitabine、troxacitabine、硫鸟嘌呤和 zebularine，似乎对治疗淋巴和骨髓恶性肿瘤有很大的潜力。然而，来自正在进行和未来临床试验的明确数据将有助于更好地确定它们在治疗血液疾病方面的地位。
