[CAS NO. 1819363-80-8]  PFI-3

PFI-3 shows a significant selectivity for PB1(5) and SMARCA2/4 over 36 other tested kinases. PFI-3 is a potent and cell active protein interaction inhibitor that selectively binds to essential BAF bromodomains. PFI-3 is screened in a commercial screening panel comprising 102 cellular receptors as well as 30 enzyme assays, revealing only interactions against four GPCRs with micromolar affinity and no significant additional interactions outside the BRD family, confirming its excellent broader pharmacological selectivity. Stability measurements confirmed that PFI-3 has a half-life in aqueous solutions exceeding 7 days at 37°C. In long-term experiments, PFI-3 significantly altered gene expression programs that are important for differentiation of stem cells. PFI-3 mimics the effect of Brg1 deletion, resulting in an increase of the repressive H3K27me3 mark at the TSSs and Stat3 binding sites of these genes. PFI-3 has a half-life of >250 h in PBS, pH 7.4, at 20 °C.