SGI-110

Cell lines

Parental A2780 cells and A2780-CDDP resistant cells

Preparation method

This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

0.1, 0.3, 1 or 5 μM; 48 hrs

Applications

At the moderate dose of 5 μM, SGI-110 increased the sensitivity of OC cells to CDDP, resulting in a > 2-fold reduction in the IC50 for CDDP: 28 μM CDDP IC50 for A2780-CDDP resistant cells and 42 μM CDDP IC50 for parental A2780 cells. SGI-110 increased the sensitivity of both the parental and the resistant A2780 cells to CDDP. It was demonstrated that SGI-110 chemosensitized the A2780 cells by demethylation and reexpression of MLH1, RASSF1A and HOXA11.

Animal models

Nude rats bearing Calu6 cells

Dosage form

20 mg/kg; s.c.; twice per week, for 4 weeks

Applications

In nude rats bearing Calu6 cells, SGI-110 alone reduced tumor burden by 35%, and the combination treatment with SGI-110 ﹢ Entinostat significantly reduced tumor burden by 56%. Besides, SGI-110 alone or in combination with Entinostat decreased the pleomorphic cell population similarly, to approximately 25%. However, compared with the control group, these 2 treatment groups showed some cumulative toxicity. After 4 weeks of treatment, body weights of rats reduced by 13 ~ 18%.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Fang F, Munck J, Tang J, Taverna P, Wang Y, Miller DF, Pilrose J, Choy G, Azab M, Pawelczak KS, VanderVere-Carozza P, Wagner M, Lyons J, Matei D, Turchi JJ, Nephew KP. The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer. Clin Cancer Res. 2014 Dec 15;20(24):6504-16.

[2]. Tellez CS1, Grimes MJ, Picchi MA, Liu Y, March TH, Reed MD, Oganesian A, Taverna P, Belinsky SA. SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome. Int J Cancer. 2014 Mar 26.