Beutler E, Carson D A
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Blood Cells. 1993;19(3):559-68; discussion 569-72.
2-Chlorodeoxyadenosine (2CdA; Cladribine; Leustatin) was developed as a result of the discovery that the death of lymphocytes in hereditary adenosine deaminase deficiency was the result of the accumulation of deoxynucleotides, specifically in lymphocytes, because of their unique enzymatic profile. This deoxyadenosine analog was selected from 25 candidate compounds because it was resistant to deamination by ADA and because it had a favorable therapeutic index. The lymphoid specific action of this drug is a function of the high deoxycytidine kinase and low 5' nucleotidase activity of lymphocytes. The drug appears to trigger apoptosis, very likely by preventing the repair of nicks in double-stranded DNA. Accordingly, 2-CdA has been found effective against a variety of lymphoid neoplasms. Hairy cell leukemia has proved to be most sensitive to its action, with approximately 80% of patients achieving a complete, long-lasting remission after a single five- or seven-day infusion. 2-CdA also shows promise in the treatment of autoimmune disorders.
2-氯脱氧腺苷（2CdA；克拉屈滨；乐疾宁）的研发源于一项发现，即遗传性腺苷脱氨酶缺乏症患者淋巴细胞的死亡是脱氧核苷酸积累的结果，特别是在淋巴细胞中，这是由于它们独特的酶谱所致。这种脱氧腺苷类似物是从25种候选化合物中挑选出来的，因为它对ADA脱氨具有抗性，并且具有良好的治疗指数。该药物的淋巴细胞特异性作用是淋巴细胞中高脱氧胞苷激酶和低5'核苷酸酶活性的结果。该药物似乎通过阻止双链DNA切口的修复来触发细胞凋亡。因此，已发现2-CdA对多种淋巴肿瘤有效。毛细胞白血病已被证明对其作用最为敏感，约80%的患者在单次5天或7天输注后可实现完全、持久的缓解。2-CdA在自身免疫性疾病的治疗中也显示出前景。
