SGI-1027

Catalog No.S7276 Batch:S727601

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Technical Data

Formula

C27H23N7O

Molecular Weight 461.52 CAS No. 1020149-73-8
Solubility (25°C)* In vitro DMSO 92 mg/mL (199.34 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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.
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

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]

In vivo

SGI-1027 (DNA Methyltransferase Inhibitor II) is a DNMT inhibitor .

Features Potential for use in epigenetic cancer therapy.

Protocol (from reference)

Kinase Assay:

[1]

  • 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 Assay:

[1]

  • 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.

Animal Study:

[3]

  • Animal Models

    Male Sprague-Dawley rats

  • Dosages

    11.2 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by Lab Chip, 2014, 14(13), 2354-62]

Data from [Data independently produced by , , Oncol Lett, 2018, 16(5):5799-5806]

Selleck's SGI-1027 has been cited by 15 publications

Bifunctional HDAC and DNMT inhibitor induces viral mimicry activates the innate immune response in triple-negative breast cancer [ Eur J Pharm Sci, 2024, 197:106767] PubMed: 38636781
Genome-wide identification of histone lysine methyltransferases and their implications in the epigenetic regulation of eggshell formation-related genes in a trematode parasite Clonorchis sinensis [ Parasites Hosts Dis, 2024, 62(1):98-116] PubMed: 38443774
DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis [ Int J Biol Sci, 2022, 18(11):4372-4387] PubMed: 35864964
Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer [ Cancers (Basel), 2022, 14(19)4883] PubMed: 36230806
Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma [ Head Neck, 2022, 44(5):1192-1205] PubMed: 35224804
Methionine Protects Mammary Cells against Oxidative Stress through Producing S-Adenosylmethionine to Maintain mTORC1 Signaling Activity [ Oxid Med Cell Longev, 2021, 2021:5550196] PubMed: 34336098
Effect of Naoluoxintong on the NogoA/RhoA/ROCK pathway by down-regulating DNA methylation in MCAO rats [ J Ethnopharmacol, 2021, 281:114559] PubMed: 34461189
Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31] PubMed: 32191458
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
Direct interaction of DNMT inhibitors to PrPC suppresses pathogenic process of prion. [ Acta Pharm Sin B, 2019, 9(5):952-959] PubMed: 31649845

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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