Pentostatin
(Synonyms: 喷司他丁; CI-825; Deoxycoformycin) 目录号 : GC12200
Pentostatin（2'-deoxycoformycin, Nipent）是一种腺苷脱氨酶抑制剂，Ki为1.2pM，IC50为1.4pM 。
Cas No.:53910-25-1
Sample solution is provided at 25 µL, 10mM.
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]。
| Kinase experiment [1]: | |
Preparation Method | Fresh dilutions of Pentostatin (0.005, 0.05, 0.125, 0.5, 5, 12.5, 50, 125, 500, 1000μM) in phosphate buffer were prepared. 30μL of 13.8mUmL−1 adenosine deaminase (ADA) and 20μL of Pentostatin were added to successive wells in a row and thoroughly mixed. In the final two wells of the row, phosphate buffer and EHNA were added, respectively, in place of Pentostatin. Two more rows were prepared in the same manner and a fourth row was prepared with phosphate buffer in place of ADA. |
Reaction Conditions | After two minutes of incubation, isothiazolo adenosine (tzA) (50μL of 7.8μM) was added and mixed thoroughly. Wells were then excited at 322nm and emission monitored at 410nm. Intensity of emission was measured every 37 seconds for just over 30 minutes. |
Applications | The IC50 value of Pentostatin is 0.0014±0.0001μM, and Ki value is 0.0012±0.0002μM |
| Cell experiment [2]: | |
Cell lines | human Primary Lymphocytes |
Preparation Method | Freeze dried Pentostatin was reconstituted with PBS, resterilized by filtration and added to cultures by pipetting on to the surface of the agar. Control cultures received the same volume of saline. Pilot experiments showed that Pentostatin was much less effective when incorporated into the agar underlay than when pipetted on to the surface. Application of Pentostatin to the agar surface had the further advantage that it could be done at any time after setting up the culture. It is however difficult to be precise about drug concentrations reaching cells by diffusion through soft agar. Cited concentrations are those pipetted on to the agar surface and are therefore all over-estimates by up to 10-fold of the concentrations surrounding the cells, since the volume of saline in which the Pentostatin was applied was one tenth that of the agar in each well. |
Reaction Conditions | 100μM-1nM; 4h |
Applications | T cells already proliferating in response to PHA are less sensitive to Pentostatin, implying that S-phase events are not primary targets of the drug's action. Colony inhibition does not appear to be due to alteration in the production of, or sensitivity to, soluble T cell growth factors. In suspension cultures, Pentostatin at concentrations up to 100μM fails to inhibit early PHA-induced volume changes, or later mitosis, in peripheral blood lymphocytes. |
| Animal experiment [3]: | |
Animal models | C57BL/6 nude mice |
Preparation Method | Mice were implanted subcutaneously with CT26/NY-ESO-1 cells and received 10μg of intravenous Pentostatin alone (“Pentostatin”) or together with 1mg intraperitoneally of an anti-IFNAR antibody (“Pentostatin + anti-IFNAR ab”) 6 days later. As controls, tumor-bearing mice received only the anti-IFNAR ab (“anti-IFNAR ab”) or were left untreated (“Untreated”) at day 6. |
Dosage form | 10μg; once; i.v |
Applications | Pentostatin can be used to treat CT26/NY-ESO-1 tumors, but its activity is abrogated by anti-IFNAR ab |
References: | |
| Cas No. | 53910-25-1 | SDF | |
| 别名 | 喷司他丁; CI-825; Deoxycoformycin | ||
| 化学名 | (8R)-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7,8-dihydro-4H-imidazo[4,5-d][1,3]diazepin-8-ol | ||
| Canonical SMILES | C1C(C(OC1N2C=NC3=C2NC=NCC3O)CO)O | ||
| 分子式 | C11H16N4O4 | 分子量 | 268.27 |
| 溶解度 | ≥ 13.4 mg/mL in DMSO, ≥ 26.8 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7276 mL | 18.6379 mL | 37.2759 mL |
| 5 mM | 0.7455 mL | 3.7276 mL | 7.4552 mL |
| 10 mM | 0.3728 mL | 1.8638 mL | 3.7276 mL |
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动物数量 | 只 |
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