Home Epigenetics DNA Methyltransferase inhibitor - Apoptosis related activator SGI-1027 For research use only.

SGI-1027

Synonyms: DNA Methyltransferase Inhibitor II

SGI-1027 (DNA Methyltransferase Inhibitor II) is a DNMT inhibitor with IC50 of 6, 8, 7.5 μM for DNMT1, DNMT3A, and DNMT3B in cell-free assays, respectively. SGI‑1027 induces apoptosis.

SGI-1027 Chemical Structure

SGI-1027 Chemical Structure

CAS No. 1020149-73-8

Purity & Quality Control

SGI-1027 Related Products

Signaling Pathway

DNA Methyltransferase Signaling Pathways

DNA Methyltransferase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human U937 cells Cytotoxicity assay 48 h Cytotoxicity against human U937 cells after 48 hrs by trypan blue exclusion assay, IC50=1.7 μM 24387159
human KARPAS299 cells Proliferation assay 2-4 days Antiproliferative activity against human KARPAS299 cells after 2 to 4 days by ATPlite 1step luminescence assay, EC50=1.8 μM 26220519
human KG1 cells Proliferation assay 2-4 days Antiproliferative activity against human KG1 cells after 2 to 4 days by ATPlite 1step luminescence assay, EC50=4.4 μM 26220519
human MDA-MB-231 cells Cytotoxicity assay 48 h Cytotoxicity against human MDA-MB-231 cells after 48 hrs by trypan blue exclusion assay, IC50=4.8 μM 24387159
human PC3 cells Cytotoxicity assay 48 h Cytotoxicity against human PC3 cells after 48 hrs by trypan blue exclusion assay, IC50=6.5 μM 24387159
human Raji cells Cytotoxicity assay 48 h Cytotoxicity against human Raji cells after 48 hrs by trypan blue exclusion assay, IC50=9.1 μM 24387159
human PBMC Cytotoxicity assay 48 h Cytotoxicity against human PBMC after 48 hrs by trypan blue exclusion assay, IC50=23.8 μM 24387159
human HCT116 cells Cytotoxicity assay Cytotoxicity against human HCT116 cells assessed as viability, TD50=25 μM 23639684
Click to View More Cell Line Experimental Data

Biological Activity

Description SGI-1027 (DNA Methyltransferase Inhibitor II) is a DNMT inhibitor with IC50 of 6, 8, 7.5 μM for DNMT1, DNMT3A, and DNMT3B in cell-free assays, respectively. SGI‑1027 induces apoptosis.
Features Potential for use in epigenetic cancer therapy.
Targets
DNMT1 [1]
(Cell-free assay)		 DNMT3B [1]
(Cell-free assay)		 DNMT3A [1]
(Cell-free assay)
6 μM 7.5 μM 8 μM
In vitro
In vitro

SGI-1027 inhibits DNA methylation by directly inhibiting DNMTs, and results in selective degradation of DNMT1 in a wide variety of human cancer cell lines. SGI-1027 exhibits minimal or no cytotoxic effect in rat hepatoma H4IIE cells. [1]

SGI-1027 (0-100 μM) exhibits a moderate pro-apoptotic effect on U937 human leukemia cell line with no relevant changes on the cell cycle. [2]
Kinase Assay DNA methyltransferase (CpG methyltransferase) assay
DNA methylase activity is assayed by measuring the incorporation of 3H1-methyl group from Ado-Met into DNA using DE-81 ion exchange filter binding assay with some modifications. Human recombinant DNMT1, recombinant mouse Dnmt3a/ Dnmt3b (500 ng) is incubated with 500 ng of poly(dI-dC) or hemimethylated DNA duplex and 75 or 150 nM (0.275μCi or 0.55μCi) of [methyl-3H]-Sadenosylmethionine (Ado-Met) in a total volume of 50 μl at 37°C for 1hr. or M. Sss I is assayed in the supplier’s buffer. Each reaction is performed in duplicate and included controls with no inhibitor or no DNA. The reaction is stopped by soaking reaction mixture onto a Whatman DE-81 ion exchange filter disc, washed (five times, 10 min each, with 0.5M Na-phosphate buffer; pH 7.0) dried and counted in a scintillation counter. The background radioactivity (no DNA control) is subtracted from the values obtained with reaction mixtures containing DNA and the radioactivity obtained in the reaction without any inhibitor is considered as 100% activity. IC50 is determined by interpolation from the plot of percent activity versus inhibitor concentration. To determine the nature of inhibition of DNMTase activity by SGI-1027, DNMT1 enzyme activityis measured in presence of a fixed concentration of inhibitor (0, 2.5, 5, and 10μM) while one of the two (Ado-Met or DNA) was 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 (25-500ng) at 75 nM Ado-Met.
Cell Research Cell lines Rat hepatoma H4IIE cells
Concentrations ~300 μM
Incubation Time 48 hours
Method

Rat hepatoma H4IIE cells are used as the test system. These 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 µmol/L. 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. The half-maximal toxic concentration (TC50) is determined from the dose-response curves.
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay Cell viability 30344731
Western blot Bcl-2 / Bax DNMT1 / TIMP3 / P16 30344731
In Vivo
In vivo

SGI-1027 (DNA Methyltransferase Inhibitor II) is a DNMT inhibitor .
Animal Research Animal Models Male Sprague-Dawley rats
Dosages 11.2 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 461.52 Formula

C27H23N7O
CAS No. 1020149-73-8 SDF Download SGI-1027 SDF
Smiles CC1=CC(=NC(=N1)N)NC2=CC=C(C=C2)NC(=O)C3=CC=C(C=C3)NC4=CC=NC5=CC=CC=C54
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 68 mg/mL ( (147.33 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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