SGI-1027
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MedKoo CAT#: 406558

CAS#: 1020149-73-8

Description: SGI-1027 is a potent DNMT inhibitor, which 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. At a concentration of 2.5 to 5 micromol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. SGI-1027 may have the potential for use in epigenetic cancer therapy.

Chemical Structure

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SGI-1027
CAS# 1020149-73-8
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406558
Name: SGI-1027
CAS#: 1020149-73-8
Chemical Formula: C27H23N7O
Exact Mass: 461.20
Molecular Weight: 461.520
Elemental Analysis: C, 70.27; H, 5.02; N, 21.24; O, 3.47

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 650 Ready to ship
200mg USD 950 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2850 Ready to ship
2g USD 5050 2 Weeks
Bulk inquiry

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

Appearance: Solid powder

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

More Info:         

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 43.30

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.

Recalculate based on batch purity %
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.

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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: García-Domínguez 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: García-Domínguez P, Weiss M, Lepore I, Ã