克拉屈滨
戊抑素
脱氧甲氧霉素
前淋巴细胞白血病
氯法拉滨
氟达拉滨
核苷类似物
嘌呤类似物
脱氧胞苷激酶
脱氧腺苷
毛细胞白血病
白血病
药理学
癌症研究
淋巴白血病
医学
核苷
慢性淋巴细胞白血病
化学
嘌呤
腺苷脱氨酶
阿糖胞苷
腺苷
免疫学
化疗
生物化学
内科学
脱氧胞苷
吉西他滨
环磷酰胺
酶
作者
Tadeusz Robak,Paweł Robak
标识
DOI:10.2174/138161212801227005
摘要
Purine nucleoside analogues (PNA) are the cytotoxic agents highly active in the treatment of indolent lymphoid malignancies. These drugs have chemical structure similar to adenosine or deoxyadenosine. PNAs are characterized by a similar mechanism of cytotoxicity both in proliferating and quiescent cells, such as inhibition of DNA synthesis, inhibition of DNA repair and accumulation of DNA strand breaks. In addition, PNAs induce apoptosis which is the end-point of their action. Older PNAs, pentostatin (DCF; 2'- deoxycoformycin), cladribine (2-CdA; 2-chloro-2'-deoxyadenosine) and fludarabine (2-fluoro-9-(-D-arabinosyl)-adenine) were approved by Food and Drug Administration (FDA) for the treatment of hematological malignancies. In addition three novel PNAs: clofarabine (CAFdA), nelarabine (ara-G) and forodesine (immucillin H, BCX-1777) have been synthesized and introduced into preclinical studies and clinical trials. This review summarizes current knowledge on the mechanism of action and pharmacokinetic properties of older and new PNAs. Clinical activity and toxicity of PNAs, especially in hairy cell leukemia (HCL), hairy cell leukemia variant (HCL-V), prolymphocytic leukemia (PLL) and other rarer chronic lymphoid leukemias, are also presented. 2-CdA and DCF, introduced in the 1980s, changed radically the treatment modality, inducing complete and durable responses in the majority of patients with HCL. In contrast, the results of the treatment of HCL-V with PNA are rather poor. There are also several reports indicating activity of PNAs in PLL and large granular lymphocyte leukemia. Clofarabine, nelarabine and forodesine need further investigation in rarer lymphid leukemias, to better define their status in the treatment of these disorders.
科研通智能强力驱动
Strongly Powered by AbleSci AI