DNA methyltransferase enzymes (DNMTs) are responsible for the DNA methylation process which could catalyze the transfer of a methyl group from S-adenosyl methionine to the cytosine target nucleotide producing methylcytosine[3]. SGI-1027 is a DNMT inhibitor with IC50 value of 0.8 µM and 10 µM on DNMT3Acat and DNMT1, respectively[4]. The RKO cells were treated with SCI-1027 at 2.5 µmol/L. The P16, MLH1 level measured by RT-PCR was reactivated after the treatment for 7 days. The protein level of P16 and TIMP3 measured by western blotting assay were also increased after 12 days of treatment while the level of DNMT1 was inhibited[5]. The cell viability of the human HCC cell line decreased in a dose dependent manner from 5 - 30 µmol after the treatment of SGI-1027 for 24 hours[6]. The C57BL/6J mice were intravitreally administered SGI-1027 10 μM in 2 μl, 24 hours before retinal injury. Only in the GLAST-positive fractions, the Oct4 expression measured by western blotting assay could be sustained after the treatment of SGI-1027[7].
作用机制
The SGI-1027 could inhibit the DNMT activity by inducing the degradation of the DNMT1 and reactivating the TSGs. It cannot bind to the RNA or the minor groove of DNA[6].
SGI-1027 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
0-100 µM
SGI-1027 inhibits the interaction between GST-MKK3 and VF-MYC
Bioorg Med Chem. 2021 Sep 1;45:116324.
DNMT1
10 µM (IC50)
2 hours
To study the mechanism of inhibition of DNMT1 by SGI-1027, results showed it as a DNA-competitive and AdoMet non-competitive inhibitor
J Biol Chem. 2015 Mar 6;290(10):6293-302.
DNMT1
10 µM (IC50)
2 hours
To study the mechanism of inhibition of DNMT1 by SGI-1027, results showed it as a DNA-competitive and AdoMet non-competitive inhibitor
J Biol Chem. 2015 Mar 6;290(10):6293-302.
HEK293 cells
10 µM
20 minutes
Evaluate the inhibitory effect of SGI-1027 and its derivatives on Rlig1-AMP, results showed that SGI-1027 and some of its derivatives effectively inhibited Rlig1-AMP activity
Chem Sci. 2025 Jan 18;16(7):3313-3322.
HeLa cells
1 µM
24 hours
To evaluate the effect of SGI-1027 in combination with AH057 on cell cycle in HeLa cells, results showed that the combined treatment increased the proportion of cells in G1 phase.
Cell Death Dis. 2020 Sep 7;11(9):724.
HeLa cells
1 µM
24 hours
To evaluate the effect of SGI-1027 in combination with AH057 on apoptosis in HeLa cells, results showed that the combined treatment significantly increased the percentage of apoptotic cells.
Cell Death Dis. 2020 Sep 7;11(9):724.
Leukemia KG-1 cells
1-10 µM
24 hours
To test the ability of the compounds to reactivate the luciferase reporter gene controlled by a methylated CMV promoter. Results showed that SGI-1027 induced a 16-fold luciferase expression at 5 μM, but at 10 μM, the signal decreased due to cytotoxicity.
ChemMedChem. 2014 Mar;9(3):590-601.
MDA-MB-231 breast cancer cells
0.9 µM
48 hours
To evaluate cell viability and proliferation, results showed that MC3353 significantly inhibited cell viability and proliferation
Clin Epigenetics. 2019 May 6;11(1):68.
PC-3 prostate cancer cells
0.9 µM
48 hours
To evaluate cell viability and proliferation, results showed that MC3353 significantly inhibited cell viability and proliferation
Clin Epigenetics. 2019 May 6;11(1):68.
RAJI Burkitt’s lymphoma cells
0.4 µM
48 hours
To evaluate cell viability and proliferation, results showed that MC3353 significantly inhibited cell viability and proliferation
Clin Epigenetics. 2019 May 6;11(1):68.
U-937 acute myeloid leukemia cells
0.4 µM
48 hours
To evaluate cell viability and proliferation, results showed that MC3353 significantly inhibited cell viability and proliferation
Clin Epigenetics. 2019 May 6;11(1):68.
HCT116 colon cancer cells
0.5 µM
48 hours
To evaluate antiproliferative activity, results showed that MC3353 significantly inhibited cell proliferation
Clin Epigenetics. 2019 May 6;11(1):68.
HK-2 cells
3.916 µM
48 hours
To evaluate the cytotoxicity of SGI-1027 on renal cancer cells and HK-2 cells, it was found that SGI-1027 inhibited the cell viability of all tested cell lines in a dose-dependent manner
Adv Sci (Weinh). 2024 Oct;11(38):e2404693.
Caki-1 cells
2.965 µM
48 hours
To evaluate the cytotoxicity of SGI-1027 on renal cancer cells and HK-2 cells, it was found that SGI-1027 inhibited the cell viability of all tested cell lines in a dose-dependent manner
Adv Sci (Weinh). 2024 Oct;11(38):e2404693.
A-498 cells
1.702 µM
48 hours
To evaluate the cytotoxicity of SGI-1027 on renal cancer cells and HK-2 cells, it was found that SGI-1027 inhibited the cell viability of all tested cell lines in a dose-dependent manner
Adv Sci (Weinh). 2024 Oct;11(38):e2404693.
786-O cells
1.121 µM
48 hours
To evaluate the cytotoxicity of SGI-1027 on renal cancer cells and HK-2 cells, it was found that SGI-1027 inhibited the cell viability of all tested cell lines in a dose-dependent manner
Adv Sci (Weinh). 2024 Oct;11(38):e2404693.
Primary osteoblasts
10 µM
48 hours
SGI-1027 alleviated the ferroptotic changes caused by FAC, but not by a GPX4 inactivator RSL3
Bone Res. 2024 Dec 2;12(1):68.
Osteoblasts
10 µM
48 hours
SGI-1027 reversed titanium particle (TP)-induced GPX4 repression and ferroptotic changes, restoring GPX4 expression and reducing the lipid peroxidation marker 4-HNE.
Research (Wash D C). 2024 Aug 19;7:0457.
SMB cells
50 nM (IC50)
5 days
Evaluate the effect of SGI-1027 on PrPSc elimination, results showed that SGI-1027 effectively eliminated PrPSc
Acta Pharm Sin B. 2019 Sep;9(5):952-959.
ScN2a cells
50 nM (IC50)
5 days
Evaluate the effect of SGI-1027 on PrPSc elimination, results showed that SGI-1027 effectively eliminated PrPSc
Acta Pharm Sin B. 2019 Sep;9(5):952-959.
KG-1 acute myeloid leukemia cells
1 µM
5 hours
To evaluate CMV promoter-driven luciferase reporter system, results showed that MC3353 significantly enhanced luciferase expression
Clin Epigenetics. 2019 May 6;11(1):68.
HK2 cells
10 µM
60 hours
Evaluate the restorative effect of SGI-1027 on KLOTHO and NRF2 expression
Aging Cell. 2022 Jan;21(1):e13526.
N2a cells
1 µM
96 hours
Evaluate the effect of SGI-1027 on prion infection prevention, results showed that SGI-1027 effectively prevented prion infection
Acta Pharm Sin B. 2019 Sep;9(5):952-959.
DNMT3Acat
0.8 µM (IC50)
To study the inhibitory activity of SGI-1027 against DNMT3Acat
J Biol Chem. 2015 Mar 6;290(10):6293-302.
DNMT3Acat
0.8 µM (IC50)
To study the inhibitory activity of SGI-1027 against DNMT3Acat
J Biol Chem. 2015 Mar 6;290(10):6293-302.
MDA-MB-468 triple-negative breast cancer cells
0-50 µM
SGI-1027 reduces MYC protein level and expression of its target genes CDK4 and PD-L1
Bioorg Med Chem. 2021 Sep 1;45:116324.
HCT116 colon cancer cells
0-50 µM
SGI-1027 inhibits MKK3-MYC protein-protein interaction, reduces MYC protein level and expression of its target genes CDK4 and PD-L1
Bioorg Med Chem. 2021 Sep 1;45:116324.
SGI-1027 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
NMDA-induced retinal injury model
Intravitreal injection
10 µM
Single injection, lasting 24 hours
SGI-1027 induced Oct4 expression in MG at 24hpi after retinal injury.
Front Neurosci. 2016 Nov 15;10:523
Mice
Ovariectomy-induced osteoporosis model
Intraperitoneal injection
2.5 mg/kg
Once daily for 6 weeks
SGI-1027 reversed promoter hypermethylation, GPX4 suppression and ferroptotic osteoporosis
Bone Res. 2024 Dec 2;12(1):68.
Mice
Calvarial osteolysis model
Intraperitoneal injection
2.5 mg/kg
Once daily for 2 weeks
SGI-1027 significantly reversed TP-induced Gpx4 promoter hypermethylation and GPX4 repression, improving ferroptotic osteolysis to a similar extent as the ferroptosis inhibitor liproxstatin-1.
Research (Wash D C). 2024 Aug 19;7:0457.
ICR mice
D-galactose-induced accelerated aging model
Intraperitoneal injection
2.5 mg/kg
Daily for 8 weeks
Evaluate the protective effect of SGI-1027 on D-gal-induced renal aging
Aging Cell. 2022 Jan;21(1):e13526.
Nude mice
A-498 cell subcutaneous xenograft model
Oral gavage
30 mg/kg/day (SGI-1027) and 2 mg/kg/day (everolimus)
Once daily for 16 days
To evaluate the in vivo anti-tumor effect of SGI-1027 in combination with everolimus, the results showed that the combination treatment significantly inhibited tumor growth and induced GSDME-dependent pyroptosis
Adv Sci (Weinh). 2024 Oct;11(38):e2404693.
BALB/c nude mice
HeLa cell xenograft model
Oral gavage
50 mg/kg/day
Once daily for 30 consecutive days
To evaluate the effect of SGI-1027 in combination with AH057 on tumor volume, results showed that the combined treatment significantly reduced tumor volume.
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