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].
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