Background:

5-Iodotubercidin (Itu) is a purine derivative and hence an inhibitor of adenosine kinase with an IC50 value of 26 nM [1].

Adenosine kinase is important in regulating the intracellular and extracellular concentrations of adenosine and hence diverse physiological actions of adenosine [2].

In various cells such as cancer cells, persisted AMPK activation could result in apoptosis [4]. In nude mice with colon carcinoma xenograft, Itu at a dose of 2.5 mg/kg resulted in rapid tumor regression compared with the control group. At the dose of 0.625 mg/kg, Itu still inhibited tumor growth, but p53-/- tumors were resistant to Itu at this lowered dose [1].

In male Wistar rat hepatocytes, incubation with Itu resulted in concentrations of AMP and ATP at 0.39 ± 0.06 and 1.51 ± 0.10 μmol/g cell wet mass, respectively; while control incubation at 0.27 ± 0.05 and 2.25 ± 0.33 μmol/g cell wet mass, respectively. Addition of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and Itu simultaneously resulted in almost the same effect of Itu alone. It was probable that Itu inhibited adenosine kinase and blocked the synthesis of 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP) from AICAR. ZAM is a structural AMP analogue and hence mimics the effect of AMP on the AMP-activated protein kinase (AMPK) activation [3].

参考文献:
[1].  Xin Zhang, Deyong Jia, Huijuan Liu, et al. Identification of 5-Iodotubercidin as a Genotoxic Drug with Anti-Cancer Potential. PLOS ONE, 2013, 8(5):e62527.
[2].  Jaoek Park and Radhey S. Gupta. Adenosine: A Key Link between Metabolism and Brain Activity: Adenosine Metabolism, Adenosine Kinase, and Evolution. New York: Springer Science+Business Media, 2013.
[3].  García-Villafranca J. and Castro J. Effects of 5-iodotubercidin on hepatic fatty acid metabolism mediated by the inhibition of acetyl-CoA carboxylase. Biochem. Pharmacol., 2002, 63(11):1997-2000.
[4].  Haiyan Chen, Ji-ping Wang, Richard J. Santen, et al. Adenosine monophosphate activated protein kinase (AMPK), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells. Apoptosis, 2015, 20:821-830.