来自CeMM分子医学研究中心、牛津大学、魏茨曼科学研究所和邓迪大学的研究团队发现，已用于治疗白血病超过70年的药物6-硫鸟嘌呤（6-TG）的作用机制存在此前未知的层面1。通过研究NUDT5蛋白，科学家发现移除该蛋白能保护细胞免受6-TG毒性影响，而仅阻断其酶活性则无此效果1。
这一发现表明NUDT5在调节硫嘌呤类药物反应中发挥的作用远超科研人员原有认识1。该蛋白不仅作为酶催化剂发挥功能，还能充当分子支架来组织细胞代谢1。研究进一步揭示，NUDT5和NUDT15两种蛋白对硫嘌呤类药物反应产生相反的影响1。这些新认识有助于解释患者对硫嘌呤类治疗的不同反应1。
Researchers have uncovered a previously unrecognized dimension to how 6-thioguanine (6-TG), a leukemia treatment used for over seventy years, exerts its therapeutic effects 1. Through investigation of the NUDT5 protein, scientists determined that removing this protein shields cells from 6-TG toxicity, whereas merely blocking its enzymatic activity does not provide such protection 1. This distinction reveals that NUDT5 influences drug response through a non-catalytic function, acting as a molecular scaffold that organizes cellular metabolism 1.
The finding helps clarify why patients respond differently to thiopurine-based therapies 1. Notably, two related proteins—NUDT5 and NUDT15—exert opposing effects on how cells respond to thiopurine drugs 1. The research collaboration involved scientists from CeMM Center for Molecular Medicine, University of Oxford, Weizmann Institute of Science, and University of Dundee 1.
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