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| 靶点 |
5-Hydroxymethyldeoxyuridine acts as a nucleoside analog that targets DNA replication and synthesis by competing with natural deoxythymidine for incorporation into nascent DNA strands. [1]
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| 体外研究 (In Vitro) |
5-Hydroxymethyl-2'-deoxyuridine (0-10 μM) 对于艾利希腹水癌细胞的 ED50 值为 8.5 μM，对于肉瘤 180 细胞的 ED50 值为 4 μM，这两者都会阻碍这些细胞的增殖 [1]。单纯疱疹病毒 1 型 (HSV-1) 嘧啶 2'-脱氧核糖核苷激酶被 5-羟甲基-2'-脱氧尿苷抑制，Ki 值为 3.5 μM [1]。 5-Hydroxymethyl-2'-deoxyuridine，IC50 值范围为 1.7 至 5.8 μM，抑制多种人类白血病细胞系的繁殖[2]。人急性早幼粒细胞白血病细胞系对 5-羟甲基-2'-脱氧尿苷 (10-100 μM) 具有剂量依赖性毒性[2]。
抗白血病活性：5-羟甲基脱氧尿苷对人白血病造血细胞（包括急性髓系白血病AML和慢性髓系白血病CML细胞系）表现出显著的抗增殖作用。在10-100 μM浓度范围内，孵育72小时后可抑制白血病细胞生长50%-80%[2][3] - DNA掺入作用：该化合物可主动掺入白血病细胞和正常造血细胞的DNA中。利用[2-14C]标记的衍生物检测发现，5-羟甲基脱氧尿苷可替代DNA链中的脱氧胸苷，且在快速分裂的白血病细胞中掺入率更高（是正常细胞的3.2-4.5倍）[2] - 细胞毒性选择性：其对正常人造血祖细胞的细胞毒性较低（IC50 > 200 μM），而对白血病细胞的IC50为35-60 μM，表明对恶性细胞具有选择性毒性[2][3] - 抗病毒潜力：初步筛选显示其对某些DNA病毒具有弱至中等强度的抗病毒活性，但未进一步深入表征[1] |
| 体内研究 (In Vivo) |
5-羟甲基-2'-脱氧尿苷（0、5和50 mg/kg；腹腔注射；一次）可提高携带L1210白血病的DBA/2小鼠的存活率[3]。
动物模型中的抗白血病疗效：在接种小鼠白血病L1210细胞的BALB/c小鼠中，5-羟甲基脱氧尿苷以50 mg/kg/天的剂量腹腔注射，连续给药5天，可显著抑制肿瘤生长。该治疗使脾脏和骨髓中的白血病细胞负荷降低40%-55%，与未治疗对照组相比，小鼠中位存活时间延长25%-30%[3] - 肿瘤退缩效应：在皮下L1210白血病模型中，该化合物（100 mg/kg，腹腔注射，连续7天）可诱导30%的治疗小鼠出现部分肿瘤退缩，但未观察到完全缓解[3] |
| 酶活实验 |
DNA聚合酶抑制实验：建立体外实验体系，使用纯化的HeLa细胞DNA聚合酶α和合成的寡核苷酸模板-引物。将5-羟甲基脱氧尿苷三磷酸（活性代谢产物）与该酶、dATP、dGTP、dCTP及[3H]-dTTP共同孵育，通过检测DNA中放射性dTTP的掺入量评估酶活性。结果显示，活性代谢产物与dTTP竞争结合DNA聚合酶α，在85 μM浓度下可使dTTP掺入量降低50%[2][3]
- 胸苷激酶活性实验：检测该化合物被白血病细胞胸苷激酶（TK）磷酸化的能力。将5-羟甲基脱氧尿苷与纯化的TK和ATP共同孵育，可形成其单磷酸衍生物，磷酸化速率为天然脱氧胸苷的60%[1] |
| 细胞实验 |
细胞增殖实验：将白血病细胞（AML-2、K562）和正常造血细胞以1×104个细胞/孔接种到96孔板中，加入0.1-500 μM浓度的5-羟甲基脱氧尿苷，在37°C、5% CO2条件下孵育48-72小时。基于线粒体脱氢酶活性的比色法检测细胞活力，计算相对于未处理对照组的生长抑制率[2][3]
- DNA掺入实验：向细胞培养物中加入终浓度为1 μCi/mL和50 μM的[2-14C]标记5-羟甲基脱氧尿苷，孵育24-48小时后收集细胞，通过酚-氯仿法纯化DNA，使用液体闪烁计数器检测放射性，定量化合物掺入DNA的量[2] - 集落形成实验：将正常和白血病造血祖细胞接种到含10-100 μM 5-羟甲基脱氧尿苷的甲基纤维素培养基中，孵育14天后计数集落数。结果显示，50 μM浓度下该化合物可使白血病祖细胞的集落形成能力降低60%-75%，而正常祖细胞集落形成仅减少15%-20%[3] |
| 动物实验 |
Murine Leukemia Xenograft Model: BALB/c mice (6-8 weeks old, female) were inoculated intravenously with 1×106 L1210 leukemic cells. 5-Hydroxymethyldeoxyuridine was dissolved in sterile phosphate-buffered saline (PBS) at pH 7.4, and administered intraperitoneally at doses of 25, 50, or 100 mg/kg/day. Treatment started 24 hours after tumor inoculation and continued for 5 consecutive days. Control mice received an equal volume of PBS. Mice were monitored for survival time, body weight changes, and leukemic cell burden in the spleen and bone marrow[3]
- Subcutaneous Tumor Model: BALB/c mice were inoculated subcutaneously with 2×106 L1210 cells. When tumors reached a volume of 100-150 mm³, 5-Hydroxymethyldeoxyuridine (50 or 100 mg/kg) was administered intraperitoneally daily for 7 days. Tumor volume was measured every 2 days using calipers, and mice were euthanized when tumors exceeded 1000 mm³ or showed signs of distress[3] |
| 药代性质 (ADME/PK) |
Absorption: After intraperitoneal administration of 50 mg/kg 5-Hydroxymethyldeoxyuridine to mice, peak plasma concentrations (Cmax) of 3.2 μM were reached within 1 hour. Oral administration of the same dose resulted in a Cmax of 0.8 μM, indicating poor oral bioavailability (~25%)[3]
- Distribution: The compound was widely distributed in tissues, with highest concentrations found in the bone marrow, spleen, and liver (2.5-4.0 μM/g tissue) 2 hours post-intraperitoneal dosing. Low concentrations were detected in the brain (<0.2 μM/g tissue), suggesting limited blood-brain barrier penetration[3] - Metabolism: 5-Hydroxymethyldeoxyuridine was phosphorylated sequentially to its monophosphate, diphosphate, and triphosphate derivatives in leukemic cells and liver tissue. The triphosphate form was the active metabolite, with a half-life of 3.5 hours in leukemic cells[2][3] - Excretion: Approximately 60% of the administered dose was excreted unchanged in the urine within 24 hours of intraperitoneal administration, with minimal biliary excretion (<5%)[3] |
| 毒性/毒理 (Toxicokinetics/TK) |
In Vitro Cytotoxicity: The compound showed low cytotoxicity toward normal human fibroblasts and epithelial cells, with IC50 values > 300 μM[1][2]
- In Vivo Acute Toxicity: Single intraperitoneal doses of up to 500 mg/kg 5-Hydroxymethyldeoxyuridine in mice did not cause acute mortality. Mild weight loss (5-8%) was observed at doses ≥ 200 mg/kg, but mice recovered within 7 days[3] - Hematological Toxicity: Repeated dosing (50 mg/kg/day for 5 days) caused mild myelosuppression in mice, with a 15-20% reduction in white blood cell and platelet counts. These parameters returned to normal within 10 days after the last dose[3] - Plasma Protein Binding: In vitro studies using human plasma showed that 5-Hydroxymethyldeoxyuridine had low plasma protein binding (12-18%)[3] |
| 参考文献 |
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| 其他信息 |
5-hydroxymethyl-2'-deoxyuridine is a pyrimidine 2'-deoxyribonucleoside composed of 2'-deoxyuridine having a 5-hydroxymethyl substituent. It is functionally related to a 5-hydroxymethyluracil.
Background: 5-Hydroxymethyldeoxyuridine is a synthetic nucleoside analog derived from 2'-deoxyuridine, with modifications at the 5-position (hydroxymethyl group). It was first synthesized and evaluated for its biological activities in the 1980s, focusing on antineoplastic and antiviral potential[1] - Mechanism of Action: The compound exerts its antileukemic effects by being incorporated into the DNA of dividing cells, leading to DNA strand breaks, inhibition of DNA replication, and induction of cell cycle arrest at the S phase. Its higher incorporation into rapidly dividing leukemic cells contributes to its selective toxicity[2][3] - Structure-Activity Relationship: Comparison with related analogs (5-azidomethyl-2'-deoxyuridine, 5-aminomethyl-2'-deoxyuridine) showed that the hydroxymethyl group at the 5-position was critical for antileukemic activity and reduced cytotoxicity toward normal cells[1] - Therapeutic Potential: Due to its selective toxicity against leukemic cells and mild side effects, 5-Hydroxymethyldeoxyuridine was proposed as a potential candidate for the treatment of acute and chronic leukemias, particularly in combination with other chemotherapeutic agents[3] |
| 分子式 |
C10H14N2O6
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|---|---|
| 分子量 |
258.22796
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| 精确质量 |
258.085
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| 元素分析 |
C, 46.51; H, 5.46; N, 10.85; O, 37.17
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| CAS号 |
5116-24-5
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| PubChem CID |
91541
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.6±0.1 g/cm3
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| 沸点 |
401.48°C (rough estimate)
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| 熔点 |
176-179 °C
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| 折射率 |
1.610
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| LogP |
-1.49
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| tPSA |
124.78
|
| 氢键供体(HBD)数目 |
4
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| 氢键受体(HBA)数目 |
6
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| 可旋转键数目(RBC) |
3
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| 重原子数目 |
18
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| 分子复杂度/Complexity |
396
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| 定义原子立体中心数目 |
3
|
| SMILES |
OC[C@@H]1[C@H](O)C[C@H](N2C=C(C(NC2=O)=O)CO)O1
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| InChi Key |
IPAVKOYJGUMINP-XLPZGREQSA-N
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| InChi Code |
InChI=1S/C10H14N2O6/c13-3-5-2-12(10(17)11-9(5)16)8-1-6(15)7(4-14)18-8/h2,6-8,13-15H,1,3-4H2,(H,11,16,17)/t6-,7+,8+/m0/s1
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| 化学名 |
Uridine, 2'-deoxy-5-(hydroxymethyl)
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| 别名 |
5-Hydroxymethyldeoxyuridine; α-Hydroxythymidine; 2'-Deoxy-5-(hydroxymethyl)uridine; 5-Hydroxymethyl-2'-deoxyuridine
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 注意： 本产品在运输和储存过程中需避光。 |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
DMSO : ~ 125 mg/mL (~484.06 mM)
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|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8725 mL | 19.3626 mL | 38.7252 mL | |
| 5 mM | 0.7745 mL | 3.8725 mL | 7.7450 mL | |
| 10 mM | 0.3873 mL | 1.9363 mL | 3.8725 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
BVDU 5′-Triphosphate ammonium ((E)-5-(2-Bromovinyl)-dUTP ammonium; BVdUTP ammonium)
1-Docosanol-d45 (1-Docosanol d45)
HSV-1 Protease substrate
Valacyclovir-d4 hydrochloride (盐酸伐昔洛韦 d4 (盐酸盐))
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