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SGI-1027

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Chemical Structure| 1020149-73-8 同义名 : DNA Methyltransferase Inhibitor II
CAS号 : 1020149-73-8
货号 : A278291
分子式 : C27H23N7O
纯度 : 99%+
分子量 : 461.518
MDL号 : MFCD27937047
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(54.17 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：

2% DMSO+30% PEG 300+2% Tween 80+water 2 mg/mL

生物活性
靶点

  • DNA Methyltransferase

    DNMT3A, IC50:7.5 μM

    DNMT1, IC50:6 μM
描述 DNA methyltransferase enzymes (DNMTs) are responsible for the DNA methylation process which could catalyze the transfer of a methyl group from S-adenosyl methionine to the cytosine target nucleotide producing methylcytosine[3]. SGI-1027 is a DNMT inhibitor with IC50 value of 0.8 µM and 10 µM on DNMT3Acat and DNMT1, respectively[4]. The RKO cells were treated with SCI-1027 at 2.5 µmol/L. The P16, MLH1 level measured by RT-PCR was reactivated after the treatment for 7 days. The protein level of P16 and TIMP3 measured by western blotting assay were also increased after 12 days of treatment while the level of DNMT1 was inhibited[5]. The cell viability of the human HCC cell line decreased in a dose dependent manner from 5 - 30 µmol after the treatment of SGI-1027 for 24 hours[6]. The C57BL/6J mice were intravitreally administered SGI-1027 10 μM in 2 μl, 24 hours before retinal injury. Only in the GLAST-positive fractions, the Oct4 expression measured by western blotting assay could be sustained after the treatment of SGI-1027[7].
作用机制 The SGI-1027 could inhibit the DNMT activity by inducing the degradation of the DNMT1 and reactivating the TSGs. It cannot bind to the RNA or the minor groove of DNA[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human HCT116 cells Cytotoxicity assay Cytotoxicity against human HCT116 cells assessed as viability, TD50=25 μM 23639684
human KARPAS299 cells Proliferation assay 2-4 days Antiproliferative activity against human KARPAS299 cells after 2 to 4 days by ATPlite 1step luminescence assay, EC50=1.8 μM 26220519
human KG1 cells Proliferation assay 2-4 days Antiproliferative activity against human KG1 cells after 2 to 4 days by ATPlite 1step luminescence assay, EC50=4.4 μM 26220519
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.83mL

2.17mL

1.08mL

21.67mL

4.33mL

2.17mL
参考文献

[1]Garcia-Dominguez P, Dell'aversana C, et al. Synthetic approaches to DNMT inhibitor SGI-1027 and effects on the U937 leukemia cell line. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1631-5.

[2]Datta J, Ghoshal K, et al. A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res. 2009 May 15;69(10):4277-85.

[3]Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science. 1975 Jan 24;187(4173):226-32.

[4]Gros C, Fleury L, Nahoum V, Faux C, Valente S, Labella D, Cantagrel F, Rilova E, Bouhlel MA, David-Cordonnier MH, Dufau I, Ausseil F, Mai A, Mourey L, Lacroix L, Arimondo PB. New insights on the mechanism of quinoline-based DNA Methyltransferase inhibitors. J Biol Chem. 2015 Mar 6;290(10):6293-302.

[5]Datta J, Ghoshal K, Denny WA, Gamage SA, Brooke DG, Phiasivongsa P, Redkar S, Jacob ST. A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res. 2009 May 15;69(10):4277-85.

[6]Sun N, Zhang J, Zhang C, Zhao B, Jiao A. DNMTs inhibitor SGI-1027 induces apoptosis in Huh7 human hepatocellular carcinoma cells. Oncol Lett. 2018 Nov;16(5):5799-5806.

[7]Reyes-Aguirre LI, Lamas M. Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury. Front Neurosci. 2016 Nov 15;10:523.