Synonym
SGI1027; SGI 1027; SGI1027.
IUPAC/Chemical Name
N-(4-((2-amino-6-methylpyrimidin-4-yl)amino)phenyl)-4-(quinolin-4-ylamino)benzamide
InChi Key
QSYLKMKIVWJAAK-UHFFFAOYSA-N
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)
SMILES Code
O=C(NC1=CC=C(NC2=NC(N)=NC(C)=C2)C=C1)C3=CC=C(NC4=CC=NC5=CC=CC=C45)C=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
SGI-1027 is a DNA methyltransferase inhibitor that inhibits the mammalian DNA methyltransferases DNMT3B, DNMT3A and DNMT1 (IC50s = 7.5, 8 and 12.5 μM, respectively, with Poly(dl-dC) as the substrate). SGI-1027 reactivates silenced tumor suppressor genes by reducing CpG island hypermethylation.
In vitro activity:
SGI-1027 can be used in the management of human hepatocellular carcinoma (HCC). It causes cell apoptosis via the mitochondrial-mediated pathway. In the Huh7 cell line, SGI-1027 treatment resulted in a significant dose-dependent decrease in cell viability. SGI-1027 resulted in cell apoptosis and typical apoptotic nucleic alterations. SGI-1027 downregulated B cell lymphoma-2 expression and upregulated Bcl-associated X protein expression. However, no significant alterations of the cell cycle phases were observed.
Reference: Oncol Lett. 2018 Nov;16(5):5799-5806. https://pubmed.ncbi.nlm.nih.gov/30344731/
In vivo activity:
Intravitreous administration of SGI-1027 induced Oct4 expression at 24 hours post-injury (hpi) in Müller glia (MG), indicating that DNA methylation may play a regulatory role in the response of MG to injury. Oct4 is rapidly expressed after retinal injury but is silenced at 24 hpi. This silencing correlates with a decrease in the expression of the Dnmt3b, returning to basal levels at 24 hpi. Changes in Oct4 methylation levels indicate that DNA methylation may restrict the injury-induced dedifferentiation of MG.
Reference: Front Neurosci. 2016 Nov 15;10:523. https://pubmed.ncbi.nlm.nih.gov/27895551/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.0 |
43.30 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
461.52
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Li JJ, Ryou CS, Kim DH. [Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells]. Mol Biol (Mosk). 2020 May-Jun;54(3):469-473. Russian. doi: 10.31857/S0026898420030118. PMID: 32492010.
2. 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. doi: 10.3892/ol.2018.9390. Epub 2018 Sep 4. PMID: 30344731; PMCID: PMC6176375.
3. Hong L, Chen W, He L, Tan H, Peng D, Zhao G, Shi X, Wang L, Liu M, Jiang H. Effect of Naoluoxintong on the NogoA/RhoA/ROCK pathway by down-regulating DNA methylation in MCAO rats. J Ethnopharmacol. 2021 Dec 5;281:114559. doi: 10.1016/j.jep.2021.114559. Epub 2021 Aug 28. PMID: 34461189.
4. 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. doi: 10.3389/fnins.2016.00523. PMID: 27895551; PMCID: PMC5108807.
In vitro protocol:
1. Li JJ, Ryou CS, Kim DH. [Effects of SGI-1027 on Formation and Elimination of PrP^(Sc) in Prion-Infected Cells]. Mol Biol (Mosk). 2020 May-Jun;54(3):469-473. Russian. doi: 10.31857/S0026898420030118. PMID: 32492010.
2. 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. doi: 10.3892/ol.2018.9390. Epub 2018 Sep 4. PMID: 30344731; PMCID: PMC6176375.
In vivo protocol:
1. Hong L, Chen W, He L, Tan H, Peng D, Zhao G, Shi X, Wang L, Liu M, Jiang H. Effect of Naoluoxintong on the NogoA/RhoA/ROCK pathway by down-regulating DNA methylation in MCAO rats. J Ethnopharmacol. 2021 Dec 5;281:114559. doi: 10.1016/j.jep.2021.114559. Epub 2021 Aug 28. PMID: 34461189.
2. 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. doi: 10.3389/fnins.2016.00523. PMID: 27895551; PMCID: PMC5108807.
1: Ronen M, Avrahami D, Gerber D. A sensitive microfluidic platform for a high throughput DNA methylation assay. Lab Chip. 2014 Jul 7;14(13):2354-62. doi: 10.1039/c4lc00150h. Epub 2014 May 19. PubMed PMID: 24841578.
2: Rilova E, Erdmann A, Gros C, Masson V, Aussagues Y, Poughon-Cassabois V, Rajavelu A, Jeltsch A, Menon Y, Novosad N, Gregoire JM, Vispé S, Schambel P, Ausseil F, Sautel F, Arimondo PB, Cantagrel F. 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. doi: 10.1002/cmdc.201300420. PubMed PMID: 24678024.
3: Fagan RL, Cryderman DE, Kopelovich L, Wallrath LL, Brenner C. Laccaic acid A is a direct, DNA-competitive inhibitor of DNA methyltransferase 1. J Biol Chem. 2013 Aug 16;288(33):23858-67. doi: 10.1074/jbc.M113.480517. Epub 2013 Jul 9. PubMed PMID: 23839987; PubMed Central PMCID: PMC3745332.
4: Gamage SA, Brooke DG, Redkar S, Datta J, Jacob ST, Denny WA. Structure-activity relationships for 4-anilinoquinoline derivatives as inhibitors of the DNA methyltransferase enzyme DNMT1. Bioorg Med Chem. 2013 Jun 1;21(11):3147-53. doi: 10.1016/j.bmc.2013.03.033. Epub 2013 Apr 6. PubMed PMID: 23639684.
5: Yoo J, Choi S, Medina-Franco JL. Molecular modeling studies of the novel inhibitors of DNA methyltransferases SGI-1027 and CBC12: implications for the mechanism of inhibition of DNMTs. PLoS One. 2013 Apr 25;8(4):e62152. doi: 10.1371/journal.pone.0062152. Print 2013. PubMed PMID: 23637988; PubMed Central PMCID: PMC3636198.
6: GarcÃa-DomÃnguez P, Dell'aversana C, Alvarez R, Altucci L, de Lera AR. 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. doi: 10.1016/j.bmcl.2013.01.085. Epub 2013 Jan 30. PubMed PMID: 23402879.
7: GarcÃa-DomÃnguez P, Weiss M, Lepore I, Ã
