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Purity: ≥98%
SGI-1027 is a novel and potent inhibitor of DNA methyltransferase (DNMT) with antineoplastic activity. It inhibits DNMT1, DNMT3A, and DNMT3B with IC50s of 6, 8, 7.5 μM in cell-free assays, respectively. SGI-1027 inhibits 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. SGI-1027 reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B.
| ln Vitro |
SGI-1027 is a DNMT inhibitor with IC50s of 7.5 μM, 8 μM and 12.5 μM for DNMT3B, DNMT3A and DNMT1 correspondingly when using poly(dI-dC) as substrate. The IC50 of SGI-1027 against DNMT1 (hemimethylated DNA) is 6 μM. SGI-1027 (1, 2.5 or 5 μM) promotes preferential degradation of DNMT1 in various human cancer cell lines but has little or no cytotoxic effect on rat hepatoma cells and does not trigger apoptosis in rat hepatoma cells [1]. SGI-1027 has an EC50 of 0.9 μM for hDNMT3A and is cytotoxic to KG-1 cells with an EC50 of 4.4 μM [2].
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| 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.
[2]. Rilova E, et al. Design, synthesis and biological evaluation of 4-amino-N- (4-aminophenyl)benzamide analogues of quinoline-based SGI-1027 as inhibitors of DNA methylation. ChemMedChem. 2014 Mar;9(3):590-601 |
| Molecular Formula |
C27H23N7O
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| Molecular Weight |
461.52
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| CAS # |
1020149-73-8
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| Related CAS # |
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| SMILES |
O=C(NC1=CC=C(NC2=NC(N)=NC(C)=C2)C=C1)C3=CC=C(NC4=CC=NC5=CC=CC=C45)C=C3
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| InChi Key |
QSYLKMKIVWJAAK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H23N7O/c1-17-16-25(34-27(28)30-17)32-20-10-12-21(13-11-20)33-26(35)18-6-8-19(9-7-18)31-24-14-15-29-23-5-3-2-4-22(23)24/h2-16H,1H3,(H,29,31)(H,33,35)(H3,28,30,32,34)
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| Chemical Name |
N-(4-((2-amino-6-methylpyrimidin-4-yl)amino)phenyl)-4-(quinolin-4-ylamino)benzamide
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| Synonyms |
DNA Methyltransferase Inhibitor II; SGI1027; SGI 1027; SGI1027;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.42 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.42 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
A, SGI-1027 induces depletion of DNMT1 in human colon cancer cell lines. C.Cancer Res.2009 May 15;69(10):4277-85. |
AtoC, SGI-1027 inhibits DNMT activity.A, DNMTase activity of M.SssI using poly (dI-dC) as substrate in presence of SGI-1027 or decitabine. The enzyme activity at different concentrations of the inhibitor was plotted against inhibitor concentration.Cancer Res.2009 May 15;69(10):4277-85. |
Methylation-specific PCR and COBRA analysis showed demethylation ofP16andTIMP3CpG island in RKO cells treated with SGI-1027.Cancer Res.2009 May 15;69(10):4277-85. |
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