9-Deazaguanine是一种嘌呤核苷类似物，具有口服活性，作为嘌呤核苷磷酸化酶(PNP)的强效抑制剂。
Cas No.:65996-58-9
Sample solution is provided at 25 µL, 10mM.
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9-Deazaguanine is a purine nucleoside analog with oral activity, functioning as a potent inhibitor of purine nucleoside phosphorylase (PNP)[1-2]. 9-Deazaguanine inhibits DNA and RNA replication by competitively inhibiting the incorporation of guanine into nucleic acid structures and interfering with the binding of guanine to proteins[3-4].
In vitro, 9-Deazaguanine and difluoromethylene phosphonic acid analogs (DFPP-DG, 9-13) (0.1–100μM) were used to treat human lymphocytes, B-cell and T-cell leukemia, and lymphoma cell lines for 72 hours. 9-Deazaguanine showed mild inhibitory activity on cell proliferation[5].
In vivo, 9-Deazaguanine (67µmoles/kg) was administered as a single intravenous injection to anesthetized Sprague-Dawley rats. 9-Deazaguanine significantly increased urine volume, sodium excretion, and glucose excretion in the rats[6].
References:
[1] Wielgus-Kutrowska B, Breer K, Hashimoto M, et al. Trimeric purine nucleoside phosphorylase: exploring postulated one-third-of-the-sites binding in the transition state. Bioorg Med Chem. 2012 Nov 15;20(22):6758-69.
[2] V T Minnow Y, Suthagar K, Clinch K, et al. Inhibition and Mechanism of Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase. ACS Chem Biol. 2022 Dec 16;17(12):3407-3419.
[3] Abu El Asrar R, Margamuljana L, Abramov M, et al. Enzymatic Incorporation of Modified Purine Nucleotides in DNA. Chembiochem. 2017 Dec 14;18(24):2408-2415.
[4] Tian G, Katchur SR, Jiang Y, et al. Small molecule-mediated allosteric activation of the base excision repair enzyme 8-oxoguanine DNA glycosylase and its impact on mitochondrial function. Sci Rep. 2022 Aug 29;12(1):14685.
[5] Glavas-Obrovac L, Suver M, Hikishima S, et al. Antiproliferative activity of purine nucleoside phosphorylase multisubstrate analogue inhibitors containing difluoromethylene phosphonic acid against leukaemia and lymphoma cells. Chem Biol Drug Des. 2010 Apr;75(4):392-9.
[6] Jackson EK, Mi Z, Kleyman TR, et al. 8-Aminoguanine Induces Diuresis, Natriuresis, and Glucosuria by Inhibiting Purine Nucleoside Phosphorylase and Reduces Potassium Excretion by Inhibiting Rac1. J Am Heart Assoc. 2018 Nov 6;7(21):e010085.
9-Deazaguanine是一种嘌呤核苷类似物，具有口服活性，作为嘌呤核苷磷酸化酶(PNP)的强效抑制剂[1-2]。9-Deazaguanine 可通过竞争性抑制鸟嘌呤掺入核酸结构并干扰鸟嘌呤与蛋白质的结合，从而抑制DNA和RNA的复制[3-4]。
在体外，9-Deazaguanine及二氟亚甲基膦酸类似物(DFPP-DG, 9-13)(0.1–100μM)处理人淋巴细胞、B细胞和T细胞白血病及淋巴瘤细胞系72小时，9-Deazaguanine细胞增殖显示出轻微的抑制活性[5]。
在体内，9-Deazaguanine(67µmoles/kg)单次静脉注射，用于处理麻醉状态下的Sprague-Dawley大鼠。9-Deazaguanine显著增加了小鼠的尿量、尿钠排泄和尿葡萄糖排泄[6]。
| Cell experiment [1]: | |
Cell lines | Human lymphocytes (Ly), chronic myeloid leukaemia in blasts crisis (K562), T-cell leukaemia (JURKAT and MOLT), T-cell lymphoma (HuT78), Burkett's lymphoma (RAJI), acute T-cell lymphoblastic leukaemia (CCRF-CEM), and acute myeloid leukaemia (HL-60) |
Preparation Method | Cells were grown in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified 5% CO₂ incubator. Exponentially growing cells were treated with 9-Deazaguanine (0.1–100μM) and its difluoromethylene phosphonic acid analogues (compounds 9-13) for 72 hours. |
Reaction Conditions | 0.1–100μM; 72h |
Applications | 9-Deazaguanine had no significant influence on lymphocyte or tumour cell growth compared to untreated controls. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Rats were anesthetized with Inactin (90mg/kg; i.p.) and surgically instrumented for hemodynamic monitoring and urine collection. After a stabilization period, a single intravenous bolus of 9-Deazaguanine (67µmoles/kg) was administered. Urine was collected during specific periods before and after administration for analysis of volume and solute excretion. |
Dosage form | 67µmoles/kg; i.v.; Single bolus. |
Applications | 9-Deazaguanine administration led to significant increases in urine volume, sodium excretion (natriuresis), and glucose excretion (glucosuria). However, unlike 8-Aminoguanine, 9-Deazaguanine did not significantly reduce potassium excretion. The diuretic, natriuretic, and glucosuric effects of 9-Deazaguanine were similar to those induced by the purine nucleoside phosphorylase (PNPase) inhibitor 8-Aminoguanine, indicating that its renal effects are mediated through the inhibition of PNPase. |
References: | |
| Cas No. | 65996-58-9 | SDF | |
| 别名 | 2-氨基-3,5-二氢吡咯并[3,2-D]嘧啶-4-酮 | ||
| Canonical SMILES | NC(N1)=NC2=C(NC=C2)C1=O | ||
| 分子式 | C6H6N4O | 分子量 | 150.1 |
| 溶解度 | DMF: 2.5 mg/ml,DMSO: 20 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: slightly soluble,PBS (pH 7.2): slightly soluble | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.6622 mL | 33.3111 mL | 66.6223 mL |
| 5 mM | 1.3324 mL | 6.6622 mL | 13.3245 mL |
| 10 mM | 666.2 μL | 3.3311 mL | 6.6622 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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