Pentostatin (2′-deoxycoformycin, Nipent) is an adenosine deaminase inhibitor with a Ki value of 1.2pM and an IC50 value of 1.4pM[1]. Pentostatin is used for hairy cell leukemia treatment, as well as another type of cancer[2]. The natural adenosine analog is produced by the bacterium Streptomyces antibioticus and the fungus Emericella nidulans[3].
In vitro, Pentostatin (100μM-1nM; 4h) inhibits the growth in soft agar of T cell colonies from PHA-stimulated human peripheral blood lymphocytes[4]. Pentostatin (1μM) also has the growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine in human cultured cell lines derived from leukemias and lymphomas[5].
In vivo, Pentostatin (10μg; once; i.v) indirectly triggers Toll-like receptor 3 and enhances immune infiltration in tumors in a C57BL/6 nude mice model[6]. Pentostatin(0.16mg/kg; once per day; 7d; i.p) also shows cytotoxicity to T cells with a decrease in the number of Thy-1-positive cells in both spleen and lymph nodes in BALB/c (H-2d) mice[7]. The effect of Pentostatin(10-100μg/g; once; s.c) on the thymus was proven to be independent of the adrenal glands by the use of adrenalectomized mice[8].
References:
[1] Adamek, Rebecca N et al. “Identification of Adenosine Deaminase Inhibitors by Metal-binding Pharmacophore Screening.” *ChemMedChem*vol. 15,22 (2020): 2151-2156. doi:10.1002/cmdc.202000271
[2] “Pentostatin.” *LiverTox: Clinical and Research Information on Drug-Induced Liver Injury*, National Institute of Diabetes and Digestive and Kidney Diseases, 12 September 2020.
[3] Agarwal, R P et al. “Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors.” *Biochemical pharmacology* vol. 26,5 (1977): 359-67. doi:10.1016/0006-2952(77)90192-7
[4] Colledge, N R et al. “Action of deoxycoformycin on human T cell colonies in vitro.” *Clinical and experimental immunology* vol. 50,1 (1982): 115-22.
[5] Kuroki, Y et al. “Potentiation of growth-inhibitory activity of 9-beta-D-arabinofuranosyladenine by 2'-deoxycoformycin in human cultured cell lines derived from leukemias and lymphomas.” *Japanese journal of cancer research : Gann* vol. 80,5 (1989): 482-9. doi:10.1111/j.1349-7006.1989.tb02340.x
[6] Tusup, Marina et al. “Epitranscriptomics modifier pentostatin indirectly triggers Toll-like receptor 3 and can enhance immune infiltration in tumors.” *Molecular therapy : the journal of the American Society of Gene Therapy* vol. 30,3 (2022): 1163-1170. doi:10.1016/j.ymthe.2021.09.022
[7] Tedde, A et al. “Animal model for immune dysfunction associated with adenosine deaminase deficiency.” *Proceedings of the National Academy of Sciences of the United States of America*vol. 77,8 (1980): 4899-903. doi:10.1073/pnas.77.8.4899
[8] Ratech, H et al. “Effects of deoxycoformycin in mice. III. A murine model reproducing multi-system pathology of human adenosine deaminase deficiency.” *The American journal of pathology* vol. 119,1 (1985): 65-72.
Pentostatin（2'-deoxycoformycin, Nipent）是一种腺苷脱氨酶抑制剂，Ki为1.2pM，IC50为1.4pM [1]。Pentostatin用于治疗毛细胞白血病，以及其他类型的癌症[2]。Pentostatin的天然腺苷类似物是由抗生素链霉菌和无灰美青霉产生的。
在体外，Pentostatin(100μM-1nM; 4h)抑制pa刺激的人外周血淋巴细胞在软琼脂中的T细胞集落生长[4]。Pentostatin（1μM）在白血病和淋巴瘤细胞系中也具有9-β-d-阿拉伯糖醛酸苷的生长抑制活性[5]。
在体内，Pentostatin(10μg; 单次给药; 静脉注射）在C57BL/6裸鼠模型中间接触发toll样受体3增强肿瘤的免疫浸润[6]。Pentostatin(10-100μg/g; 单次; 腹腔注射)在BALB/c (H-2d)小鼠模型中导致脾脏和淋巴结中thy -1阳性细胞数量减少，显示出Pentostatin对T细胞的细胞毒性[7]。Pentostatin (10-100μg/g; 单次; 皮下注射) 通过使用切除肾上腺的小鼠证明Pentostatin的作用机制独立于肾上腺[8]。