Furman Richard R, Hoelzer Dieter
CLL Research Center, Weill Cornell Medical Center, New York, NY 10021, USA.
Semin Oncol. 2007 Dec;34(6 Suppl 5):S29-34. doi: 10.1053/j.seminoncol.2007.11.004.
Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of ribonucleosides and 2'-deoxyribonucleosides to their respective bases. Endogenous PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease that has prompted the development of PNP inhibitors as potential therapies for T-cell-mediated diseases. PNP inhibition leads to the elevation of 2'-deoxyguanosine levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing cellular apoptosis. Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that has shown activity in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma. Additional preliminary findings support its use for the management of some B-cell malignancies.
嘌呤核苷磷酸化酶（PNP）催化核糖核苷和2'-脱氧核糖核苷可逆地磷酸解为各自的碱基。内源性PNP缺乏会导致特异性T细胞免疫缺陷，这是一种遗传性疾病，促使人们开发PNP抑制剂作为T细胞介导疾病的潜在治疗方法。PNP抑制会导致2'-脱氧鸟苷水平升高和细胞内脱氧鸟苷5'-三磷酸积累，从而诱导细胞凋亡。福多司坦是一种高效、口服活性、合理设计的PNP抑制剂，在针对恶性细胞的临床前研究中显示出活性，并对T细胞急性淋巴细胞白血病和皮肤T细胞淋巴瘤具有临床应用价值。其他初步研究结果支持将其用于治疗某些B细胞恶性肿瘤。
