Nitrobenzylthioinosine (NBMPR) is an inhibitor of the equilibrative nucleoside transporter subtype 1 (ENT1) transporter, which binds to the ENT1 transporter with high affinity[1, 2]. Nitrobenzylthioinosine can inhibit adenosine reuptake by inhibiting the ENT1 transporter, and has anti-inflammatory, cardioprotective, and neuroprotective effects[3]. Nitrobenzylthioinosine is a photoaffinity probe that can be used to track adenosine uptake sites in the brain and can cross the blood-brain barrier[4].
In vitro, treatment of HeLa cells with Nitrobenzylthioinosine (5μM) inhibited the uptake of uridine by the cells, but had no effect on uridine kinase in HeLa cell extracts or the relative proportions of uridine anabolic metabolites in intact cells[5].
In vivo, Nitrobenzylthioinosine (50, 100mg/kg) was intraperitoneally injected into mice bearing B16 melanoma cells for 4 days, and combined with N-phosphonoacetyl-L-aspartic acid (PALA) was able to inhibit melanoma growth in mice[6].
References:
[1] Zhang Y W, Shepel P N, Peeling J, et al. Effects of nitrobenzylthioinosine on adenosine levels and neuronal injury in rat forebrain ischemia[J]. Neuroscience Research Communications, 2002, 30(2): 83-89.
[2] Rehan S, Shahid S, Salminen T A, et al. Current progress on equilibrative nucleoside transporter function and inhibitor design[J]. SLAS DISCOVERY: Advancing Life Sciences R&D, 2019, 24(10): 953-968.
[3] Li R W S, Yang C, Sit A S M, et al. Physiological and pharmacological roles of vascular nucleoside transporters[J]. Journal of cardiovascular pharmacology, 2012, 59(1): 10-15.
[4] Kalaria R N, Harik S I. Nucleoside Transporter of Cerebral Micro vessels and Choroid Plexus[J]. Journal of neurochemistry, 1986, 47(6): 1849-1856.
[5] PATERSON A R P, NAIK S R, CASS C E. Inhibition of uridine uptake in HeLa cells by nitrobenzylthioinosine and related compounds[J]. Molecular Pharmacology, 1977, 13(6): 1014-1023.
[6] Erlichman C, Vidgen D. Antitumor activity of N-phosphonacetyl-L-aspartic acid in combination with nitrobenzylthioinosine[J]. Biochemical pharmacology, 1984, 33(20): 3177-3181.
Nitrobenzylthioinosine (NBMPR)是一种平衡型核苷转运子亚型1（ENT1）转运蛋白抑制剂，以高亲和力与ENT1转运蛋白结合[1, 2]。Nitrobenzylthioinosine能够通过抑制ENT1转运蛋白从而抑制腺苷再摄取，具有抗炎、心脏保护、神经保护作用[3]。Nitrobenzylthioinosine是一种光亲和探针，能够用于追踪大脑中腺苷的摄取位点，可以穿过血脑屏障[4]。
在体外，Nitrobenzylthioinosine（5μM）处理HeLa细胞，抑制了细胞对尿苷的摄取，对HeLa细胞提取物中的尿苷激酶或完整细胞中尿苷合成代谢物的相对比例没有影响[5]。
在体内，Nitrobenzylthioinosine（50, 100mg/kg）通过腹腔注射治疗B16黑色素瘤细胞异种移植小鼠4天，联合N-膦乙酰基-L-天冬氨酸（PALA）能够抑制小鼠体内黑色素瘤生长[6]。