SGI-1027 (Synonyms: DNA Methyltransferase Inhibitor II) |
| Catalog No.GC14364 |
SGI-1027 es un inhibidor de la ADN metiltransferasa (DNMT), con IC50 de 7,5 μM, 8 μM y 12,5 μM para DNMT3B, DNMT3A y DNMT1 con poli(dI-dC) como sustrato.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1020149-73-8
Sample solution is provided at 25 µL, 10mM.
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SGI-1027 is an inhibitor of DNMT with IC50 values of 12.5μM, 8μM and 7.5μM, respectively for DNMT1, DNMT3A and DNMT3B [1].
SGI-1027 shows inhibition with mammalian DNMTs and bacterial M. SssI in vitro. Both the endogenous and recombinant DNMTs can be inhibited by SGI-1027. The mechanism of this inhibition is that SGI-1027 competes with Ado-Met but not the substrate DNA within the cofactor binding site of the enzyme. SGI-1027 inhibits DNA methylation through directly inhibiting DNMTs [1].
In cancer cells, many TSGs are silenced due to hypermethylation of CpG islands in their promoters. SGI-1027 can demethylates these CpG islands and reactivate the silenced TSGs. In RKO cells, prolonged treatment of SGI-1027 induces reexpression of P16 and TIMP3 genes. Moreover, SGI-1027 is found to cause selective degradation of DNMT1 via proteasomal pathway [1].
References:
[1] 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.
Kinase experiment: | To determine the nature of inhibition of DNMTase activity by SGI-1027, DNMT1 enzyme activity is measured in presence of a fixed concentration of SGI-1027 (0, 2.5, 5, and 10 μM) while one of the two (Ado-Met or DNA) is varied in a particular reaction mixture. At a fixed concentration of DNA (500 ng) varying concentrations of Ado-Met used are from 25-500 nM, respectively. Similarly, final DNA concentrations are varied from (25-500 ng) at 75 nM Ado-Met[1]. |
Cell experiment: | Rat hepatoma H4IIE cells are grown in DMEM supplemented with fetal bovine serum (10%) and calf serum (10%). Cells are seeded into 96-well plates and after 48 h exposed to SGI-1027 at concentrations ranging from 0 to 300 µM. The solubility is determined by Nephalometry techniques immediately after dosing and before harvesting the cells at 24 h. Following the exposure period, the cells or their supernatant (culture medium) are analyzed for changes in cell proliferation (propidium iodide), membrane leakage (α-GST), mitochondrial function [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cellular ATP], oxidative stress (intracellular GSH and 8-isoprostane), and apoptosis (caspase-3). The half-maximal toxic concentration (TC50) is determined from the dose-response curves[1]. |
References: [1]. Datta J, 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. | |
| Cas No. | 1020149-73-8 | SDF | |
| Sinónimos | DNA Methyltransferase Inhibitor II | ||
| Chemical Name | N-[4-[(2-amino-6-methylpyrimidin-4-yl)amino]phenyl]-4-(quinolin-4-ylamino)benzamide | ||
| Canonical SMILES | CC1=CC(=NC(=N1)N)NC2=CC=C(C=C2)NC(=O)C3=CC=C(C=C3)NC4=CC=NC5=CC=CC=C54 | ||
| Formula | C27H23N7O | M.Wt | 461.52 |
| Solubility | ≥ 22.25mg/mL in DMSO with gentle warming | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1668 mL | 10.8338 mL | 21.6675 mL |
| 5 mM | 0.4334 mL | 2.1668 mL | 4.3335 mL |
| 10 mM | 0.2167 mL | 1.0834 mL | 2.1668 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)
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