6-Thioguanine

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Chemical Structure| 154-42-7 同义名 : 硫鸟嘌呤 ;Thioguanine;2-Amino-6-purinethiol;6Mercapto2aminopurine;6HPurine6thione 2amino17dihydro (9CI);6 Thioguanine;6 Mercaptoguanine;2Amino 6MP;WR1141;BW 5071;Tabloid;6-TG;NSC 76504;NSC 752
CAS号 : 154-42-7
货号 : A393548
分子式 : C5H5N5S
纯度 : 98%
分子量 : 167.192
MDL号 : MFCD02730136
存储条件：

Pure form Keep in dark place,Inert atmosphere,Room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(53.83 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 3% DMSO+3% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 61 mg/mL suspension

生物活性
靶点

  • DNA Methyltransferase
描述 The DNA methyltransferase (DNMT) family are enzymes that can catalyze the transfer of methyl group to DNA using S-adenosylmethionine (SAM) as a methyl donor with subsequent conversion of SAM to S-adenosylhomocysteine (SAH). Inhibiting the DNMTs have shown particular promise in the treatment of haematological malignancies[1]. Thioguanine which is used for the therapy of acute leukemia could inhibit the DNMT1.
On both canine large T cell leukemia line CLGL-90 and B cell line CLL 17-7, after incubating with thioguanine at 1.5, 3.0 and 6.0 μM for 24 hours, DNMT1 expression measured was reduced. Global methylation also demonstrated significant decreases following treatment of 6.0 μM thioguanine[2]. Similar results could be seen on Jurkat T cells. When the cells were treated with 1 - 3 μM of thioguanine for 24 hours, the percentage of cytosine methylation showed a decrease from 3.92% to 3.39% with 3 μM of thioguanine[3].
In VC8 cells injected CD1 nude mice cancer model, 1.5 mg/kg of thioguanine was administered i.p. daily for ten days. The tumor growth was significantly delayed after the treatment of thioguanine[4].
作用机制 After exposing to thioguanine, the DNMT1 is shifted toward ubiquination-mediated proteasomal degradation via alteration of the expression of histone lysine-specific demethylase[2].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03334266 Obesity Infan... 展开 >>t Obesity Mother-Child Relations Dietary Habits Breast Feeding Physical Activity Childhood Obesity Feeding Behavior 收起 << Not Applicable Recruiting December 31, 2021 United States, Arizona ... 展开 >> Johns Hopkins Center for American Indian Health Recruiting Fort Defiance, Arizona, United States, 86504 Contact: Allison Barlow, PhD    410-955-6931    abarlow@jhu.edu    Contact: Nicole Neault, MPH    5057973309    nneault@jhu.edu    Johns Hopkins Center for American Indian Health Recruiting Whiteriver, Arizona, United States, 85941 Contact: Allison Barlow, PhD    410-955-6931    abarlow@jhu.edu    Contact: Nicole Neault, MPH    5057973309    nneault@jhu.edu    United States, New Mexico Johns Hopkins Center for American Indian Health Recruiting Shiprock, New Mexico, United States, 87420 Contact: Allison Barlow, PhD    410-955-6931    abarlow@jhu.edu    Contact: Nicole Neault, MPH    5057973309    nneault@jhu.edu 收起 <<
NCT02281799 Pancreatitis ... 展开 >>Inflammatory Bowel Diseases 收起 << Phase 4 Recruiting January 2019 Israel ... 展开 >> Shaare Zedek Recruiting Jerusalem, Israel, 91031 收起 <<
NCT02046694 Acute Lymphoblastic Leukemia (... 展开 >>ALL) 收起 << Early Phase 1 Recruiting September 2021 United States, Maryland ... 展开 >> Johns Hopkins Hospital Recruiting Baltimore, Maryland, United States, 21287 Principal Investigator: Colleen Annesley, MD          Sub-Investigator: Patrick A Brown, MD          United States, Texas Texas Children's Cancer and Hematology Centers Recruiting Houston, Texas, United States, 77030 Contact: Julie Brackett, MD    832-822-4242       Sub-Investigator: Edward Sisson, MD          Principal Investigator: Julie Brackett, MD          United States, Washington Seattle Children's Hospital Recruiting Seattle, Washington, United States, 98105 Contact: Colleen Annesley, MD          Principal Investigator: Colleen Annesley, MD 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

5.98mL

1.20mL

0.60mL

29.91mL

5.98mL

2.99mL

59.81mL

11.96mL

5.98mL
参考文献

[1]Hogarth LA, Redfern CP, et al. The effect of thiopurine drugs on DNA methylation in relation to TPMT expression. Biochem Pharmacol. 2008;76(8):1024-35.

[2]Flesner BK, Kumar SR, et al. 6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells. BMC Vet Res. 2014.

[3]Wang H, Wang Y. 6-Thioguanine perturbs cytosine methylation at the CpG dinucleotide site by DNA methyltransferases in vitro and acts as a DNA demethylating agent in vivo. Biochemistry. 2009;48(10):2290-9.

[4]Issaeva N, Thomas HD, et al. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res. 2010;70(15):6268-76.