Guadecitabine sodium
(Synonyms: SGI-110 sodium; S-110 sodium) 目录号 : GC36196
Guadecitabine 是地西他滨和脱氧鸟苷的新型低甲基化二核苷酸，可抵抗胞苷脱氨酶的降解。
Cas No.:929904-85-8
Sample solution is provided at 25 µL, 10mM.
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Guadecitabine is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine that is resistant to degradation by cytidine deaminase. Guadecitabine Sodium is the easily dissolved form of Guadecitabine[1].
Guadecitabine (0.1, 0.3, 1, 5μM, 48h) increased sensitivity to cisplatin for both the parental and the resistant A2780 cells. Although among other ovarian cancer cell lines, the parental A2780- cisplatin resistant cells is considered to be cisplatin “sensitive”, it has a relatively high IC50 for the drug[2].
Guadecitabine (50nM-2μM, 24h) pretreatment synergistically interacted with ASTX660 to induce cell death in five AML cell lines (MOLM-13, ML-2, MV4-11, PLB-985, KG-1) with various genetic backgrounds and representing different AML subtypes?[3].
Tumor-bearing immune-deficient mice were exposed subcutaneously to Guadecitabine at doses of 3, 6.1, or 10 mg/kg, daily for 5 days, with tumors harvested on day 7. Most mice treated on the 5 day schedule with 10mg/kg/day Guadecitabine died; all mice treated with 6.1mg/kg/day Guadecitabine developed gastrointestinal toxicity. Minimal toxicity was observed in mice treated with 3mg/kg/day. Guadecitabine treatment caused hypomethylation of?LINE-1?and?NY-ESO-1?at all doses[4].
References:
[1].Issa JJ, Roboz G, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015 Sep;16(9):1099-1110.
[2].Fang F, Munck J, et al. The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer. Clin Cancer Res. 2014 Dec 15;20(24):6504-16.
[3].Dittmann J, Haydn T, et al. Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways. Cell Death Differ. 2020 Jun;27(6):1878-1895.
[4].rivastava P, Paluch BE, et al. Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells and xenografts. Leuk Res. 2014 Nov;38(11):1332-41.
Guadecitabine 是地西他滨和脱氧鸟苷的新型低甲基化二核苷酸,可抵抗胞苷脱氨酶的降解。 Guadecitabine Sodium 是 Guadecitabine 的易溶解形式[1]。
Guadecitabine (0.1, 0.3, 1, 5μM, 48h) 增加了亲本细胞和耐药 A2780 细胞对顺铂的敏感性。尽管在其他卵巢癌细胞系中,亲本 A2780-顺铂耐药细胞被认为对顺铂"敏感",但其对该药物具有相对较高的 IC50[2]。
Guadecitabine (50nM-2μM, 24h) 预处理与 ASTX660 协同作用,在具有不同遗传背景的五种 AML 细胞系（MOLM-13、ML-2、MV4-11、PLB-985、KG-1）中诱导细胞死亡并代表不同的 AML 子类型[3]。
携带肿瘤的免疫缺陷小鼠皮下暴露于剂量为 3、6.1 或 10 mg/kg 的瓜地西他滨,持续 5 天,并在第 7 天收获肿瘤。大多数小鼠在 5 天的治疗方案中接受 10mg /kg/day 瓜地西他滨死亡；所有用 6.1mg/kg/天 Guadecitabine 治疗的小鼠都出现了胃肠道毒性。在用 3mg/kg/天处理的小鼠中观察到最小毒性。瓜地西他滨治疗导致所有剂量的 LINE-1 和 NY-ESO-1 低甲基化[4]。
| Cell experiment [1]: | |
|
Cell lines |
Leukemic cell lines(HL60, KG1a, U937) |
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Preparation Method |
To evaluate the effect of Guadecitabine treatment on Cancer Testis Antigen methylation, HL60, U937, and KG1a leukemic cell lines were treated with Guadecitabine and harvested on day 5. |
|
Reaction Conditions |
Leukemic cell line were treated with Guadecitabine ( 0.1, 1.0 and 5μM) for 5 days. |
|
Applications |
Guadecitabine treatment resulted in significant reductions of LINE-1 and NY-ESO-1 promoter methylation in HL60, U937 and KG1a cells, as determined by quantitative bisulfite pyrosequencing.MAGE-A3/6 was also hypomethylated following Guadecitabine treatment in all cell lines. |
| Animal experiment [2]: | |
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Animal models |
SCID mice |
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Preparation Method |
OVCAR3 cells were implanted into the hindquarters of SCID mice. After 2–3 weeks, when macroscopic tumors were formed, mice were treated with Guadecitabine for 5day. |
|
Dosage form |
3 mg/kg/day, subcutaneous treatment |
|
Applications |
OVCAR3 tumors were treated with 3 mg/kg/d, 5 days Guadecitabine or vehicle control subcutaneously, 3 days later, injected with NY-ESO-1-specific CD8+ T-cells or vehicle control (PBS) intra-tumorally. The combination of Guadecitabine and NY-ESO-1 specific T-cells showed delayed tumor growth in comparison with mice treated with Guadecitabine or NY-ESO-1-specific CD8 +T-cells alone.these data suggest Guadecitabine treatment enhances NY-ESO-1-specific antitumor responses in vivo. |
|
References: [1]. Srivastava P, Paluch BE,et al. Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells and xenografts. Leuk Res. 2014 Nov;38(11):1332-41. [2]. Srivastava P, Paluch BE,et al. Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46. |
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| Cas No. | 929904-85-8 | SDF | |
| 别名 | SGI-110 sodium; S-110 sodium | ||
| Canonical SMILES | O=C1C2=C(N([C@H]3C[C@H](O)[C@@H](COP(O[C@@H]4[C@@H](CO)O[C@@H](N5C=NC(N)=NC5=O)C4)([O-])=O)O3)C=N2)NC(N)=N1.[Na+] | ||
| 分子式 | C18H23N9NaO10P | 分子量 | 579.39 |
| 溶解度 | DMSO: 50 mg/mL (86.30 mM); 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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| 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 | 1.726 mL | 8.6298 mL | 17.2595 mL |
| 5 mM | 0.3452 mL | 1.726 mL | 3.4519 mL |
| 10 mM | 0.1726 mL | 0.863 mL | 1.726 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet