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核糖核苷酸还原酶抑制剂在血液系统恶性肿瘤中的作用演变

Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies.

作者信息

Tsimberidou Apostolia-Maria, Alvarado Yesid, Giles Francis J

机构信息

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston 77030, USA.

出版信息

Expert Rev Anticancer Ther. 2002 Aug;2(4):437-48. doi: 10.1586/14737140.2.4.437.

Abstract

Ribonucleotide reductases catalyze the de novo biosynthesis of deoxyribonucleosides for DNA synthesis. Increased ribonucleotide reductases activity has been associated with malignant transformation and tumor cell growth. The ribonucleotide reductases inhibitors may bind with the R1 subunit of the enzyme (Class 1) or the nonheme iron (Class 2). This review focuses on the therapeutic use of ribonucleotide reductases inhibitors in hematologic malignancies. Hydroxyurea, fludarabine and cladribine have established roles in the management of hematologic malignancies, while other ribonucleotide reductases inhibitors, such as gemcitabine, tezacitabine and heterocyclic carboxaldehyde thiosemicarbazones (e.g., triapine) are being evaluated in clinical trials.

摘要

核糖核苷酸还原酶催化脱氧核糖核苷的从头生物合成以用于DNA合成。核糖核苷酸还原酶活性增加与恶性转化和肿瘤细胞生长有关。核糖核苷酸还原酶抑制剂可与该酶的R1亚基结合(1类)或与非血红素铁结合(2类)。本综述重点关注核糖核苷酸还原酶抑制剂在血液系统恶性肿瘤中的治疗应用。羟基脲、氟达拉滨和克拉屈滨在血液系统恶性肿瘤的治疗中已确立了作用,而其他核糖核苷酸还原酶抑制剂,如吉西他滨、替扎西他滨和杂环羧醛硫代半卡巴腙(如曲阿普明)正在临床试验中进行评估。

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