PFI-1 is a novel potent, selective and cell permeable inhibitor of the bromodomain and extra terminal (BET) family proteins BRD2 and BRD4 with IC50 of ~98 nM and 220 nM respectively. Co-crystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD2 and BRD4. It has an EC50 of 1.89 μM for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS. PFI-1 induces dose-dependent reduction of cell viability in T4302 CD133+ cells, inhibits the proliferation of three NET cell lines (Bon-1 derived from a pancreatic NET, and H727 and H720 derived from lung NETs). It was also shown that PFI-1 could significantly down-regulate Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10.