PFI-3, a potent and cell-permeable probe, effectively displaces ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin. It exhibits strong binding to both SMARCA2 and SMARCA4 bromodomains (The KD of the BROMOScan ranges from 55 to 110 nM), consistent with the measured binding constant (KD=89 nM) determined by isothermal titration calorimetry. However, PFI-3 fails to mimic the growth-inhibitory effects observed with SMARCA2 knockdown in lung cancer [1]. Treating embryonic stem cells with PFI-3 results in loss of stemness and disruption of lineage specification. Additionally, PFI-3 significantly boosts the differentiation of trophoblast stem cells [2]. PFI-3 selectively targets specific family VIII bromodomains while maintaining significant overall bromodomain family selectivity. Its unique binding mode, involving a phenolic headgroup, disrupts water molecules typically retained by other bromodomain inhibitors, contributing to its high specificity for family VIII [3].
体外研究
PFI-3, a potent and cell-permeable probe, effectively displaces ectopically expressed, GFP-tagged SMARCA2-bromodomain from chromatin. It exhibits strong binding to both SMARCA2 and SMARCA4 bromodomains (The KD of the BROMOScan ranges from 55 to 110 nM), consistent with the measured binding constant (KD=89 nM) determined by isothermal titration calorimetry. However, PFI-3 fails to mimic the growth-inhibitory effects observed with SMARCA2 knockdown in lung cancer [1].
Treating embryonic stem cells with PFI-3 results in loss of stemness and disruption of lineage specification. Additionally, PFI-3 significantly boosts the differentiation of trophoblast stem cells [2].
PFI-3 selectively targets specific family VIII bromodomains while maintaining significant overall bromodomain family selectivity. Its unique binding mode, involving a phenolic headgroup, disrupts water molecules typically retained by other bromodomain inhibitors, contributing to its high specificity for family VIII [3].
PFI-3 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Ea.hy926 cells
2 μM
24 h
PFI-3 significantly decreased TNF-α-induced IL-1β and CCL2 expression
Front Cell Dev Biol. 2020 Nov 30;8:578790.
Neural Stem Cells
10 µM
5 days
PFI-3 treatment resulted in neurosphere-like formation and loss of self-renewal in neural stem cells.
Stem Cell Reports. 2019 May 14;12(5):1084-1098.
AdvSca1-SM cells
50 μM
72 h
PFI-3 blocked TGF-β1–induced differentiation of AdvSca1-SM cells into myofibroblasts and reduced collagen contraction.
JCI Insight. 2023 May 8;8(9):e164862.
HEK293T cells
5 μM
10 min
To evaluate the effect of PFI-3 on translation, results showed that 10-minute inhibition significantly reduced translation levels.
Cancer Res. 2022 Aug 16;82(16):2829-2837.
HEK293T cells
5 μM
24 h
To evaluate the effect of PFI-3 on translation, results showed that 24-h inhibition significantly reduced translation levels.
Cancer Res. 2022 Aug 16;82(16):2829-2837.
neonatal mouse cardiomyocytes
10 μM
24 h
After Brg1 inhibition, the protein level of TRPM4 was reduced
Front Pharmacol. 2024 Dec 12;15:1494205.
Rh30 cells
10 μM
24 h
Inhibition of SMARCA4 bromodomain activity increased miR-27a expression.
Sci Signal. 2018 Nov 20;11(557):eaau7632.
zebra fish embryos
100 μM
3.5 hpf
Inhibit Smarca2 function, accelerate H3K9me3 establishment and chromatin compaction
Nat Commun. 2019 Apr 4;10(1):1551.
AdvSca1-SM cells
50 μM
72 h
PFI-3 inhibited TGF-β1-induced differentiation of AdvSca1-SM cells into myofibroblasts, reduced the expression of Acta2, Postn, and Mrtfa, and inhibited collagen gel contraction.
JCI Insight. 2023 May 8;8(9):e164862.
PFI-3 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Gli1-CreERT2 ROSA-YFP AdvSca1-SM reporter mice
Oral gavage
50 mg/kg
Every 4 days for 4 weeks
PFI-3 inhibited the Brg1 bromodomain, reducing injury-induced vascular remodeling and fibrosis.
JCI Insight. 2023 May 8;8(9):e164862.
Mice
Gli1-CreERT2 ROSA-YFP AdvSca1-SM reporter mice
Oral gavage
50 mg/kg
Every 4 days for 4 weeks
PFI-3 inhibited the Brg1 bromodomain, reducing pathological vascular remodeling induced by carotid artery ligation, including decreased neointima area, adventitial expansion, and collagen deposition.
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