Somatic mutation and amplification of histone methyltransferases are commonly observed in human cancers. BRD4770 is a selective, small-molecule inhibitor of histone methyltransferase G9a. The IC50 value of its active form (BRD9539) for G9a activity in cells is 6.3μM. Treatment of PANC-1 cells with 10μM BRD4770 for 24 hours resulted in a significant decrease in di- and trimethylation levels of H3K9, as well as an increase in monomethylation level. Treatment of PANC-1 cells with 5μM BRD4770 for 24 hours decreased trimethylation level of H3K9 by 23%. The EC50 values of BRD4770 for trimethylated H3K9 in PANC-1 cells were ~5μM. BRD4770-treated PANC-1 cells also showed increased cell population in G2/M and decreased G0/G1 cell fraction compared with DMSO-treated controls[3]. The subcutaneous injection of BRD4770 (10mg/kg, three times per week on days 1, 3, and 5) combined with prexasertib (2mg/kg, injection for three days followed by four-day off) inhibited the growth of subcutaneous L3.6 xenografts in mice[4].
BRD4770 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PANC-1 cells
2.5 μM
3 days
induces senescence and cell death, dependent on p53 status
Cell Death Dis. 2013 Jun 27;4(6):e690.
mouse embryo fibroblasts (MEFs)
20 μM
48 h
BRD4770 augmented Keap1 and NF-κB p50 binding and inhibited H3K9me2 deposition at virus induced genes in MEFs with intact Keap1.
Immunology. 2022 Sep;167(1):105-121
LIPC cells
1.25 and 2.5μM
To evaluate the effect of BRD4770 in combination with prexasertib on LIPC cell growth, showing synergistic reduction in cell viability.
Mol Cancer Res. 2020 Mar;18(3):448-462
Mia-Paca2 cells
0.62–2.5μM
72 h
To evaluate the effect of BRD4770 alone on Mia-Paca2 cell growth, showing partial inhibition of cell growth within 72 h.
Mol Cancer Res. 2020 Mar;18(3):448-462
L3.6 cells
0.62–2.5μM
72 h
To evaluate the effect of BRD4770 alone on L3.6 cell growth, showing partial inhibition of cell growth within 72 h.
Mol Cancer Res. 2020 Mar;18(3):448-462
BxPC3 cells
0.62–2.5μM
72 h
To evaluate the effect of BRD4770 alone on BxPC3 cell growth, showing partial inhibition of cell growth within 72 h.
Mol Cancer Res. 2020 Mar;18(3):448-462
Diaporthe longicolla
100 nM
21 days
To evaluate the effect of BRD4770 on the metabolic profiling of Diaporthe longicolla, results showed increased inhibition zone against S. aureus and MRSA, and enhanced antioxidant activity in the crude extract from cultures treated with 100 nM BRD4770.
Front Microbiol. 2021 Sep 17;12:725463
PANC-1 cells
5 μM
24 h
BRD4770 reduced di- and trimethylation levels of H3K9 and increased monomethylation level without inducing apoptosis
ACS Chem Biol. 2012 Jul 20;7(7):1152-7
Primary human aortic vascular smooth muscle cells (p-HAVSMCs)
5 μM
48 h
To evaluate the effect of BRD4770 on p-HAVSMCs proliferation, results showed that BRD4770 inhibited cell proliferation by blocking G2/M phase.
To evaluate the effect of BRD4770 on RAVSMCs proliferation, results showed that BRD4770 inhibited cell proliferation by blocking G2/M phase.
Hum Cell. 2023 Sep;36(5):1672-1688
BRD4770 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Carotid artery wire injury model
Intraperitoneal injection
1 mg/kg
Once daily for 28 days
To evaluate the effect of BRD4770 on vascular intimal hyperplasia, results showed that BRD4770 significantly alleviated restenosis of injured carotid arteries.
Hum Cell. 2023 Sep;36(5):1672-1688
NU/J mice
Subcutaneous and orthotopic xenograft models
Subcutaneous injection
10mg/kg
3 times per week for 14 days
To evaluate the effect of BRD4770 alone or in combination with prexasertib on subcutaneous and orthotopic xenograft models, showing significant reduction in tumor growth with combination therapy.
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