Brief Description

PFI-1 can efficiently block the interaction of BET BRDs with H3 and H4 acetylated histone tails.
IC50 Value: 1.89 nM (EC50 for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS)
Target: BET BRDs
Inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer.
in vitro: Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, The compound showed <50% inhibition against a panel of 15 targets made up of GPCRs, ion channels, and enzymes at 10 μM at Cerep and <20% inhibition against 50 kinases at 1 μM at Invitrogen. Cell-based activity was tested in an LPS challenge assay in PBMCs. Compound 17 had an EC50 of 1.89 μM (n = 6) for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS.
in vivo: Rodent pharmacokinetics for PFI-1 were studied in both rat (1 mg/kg iv and 2 mg/kg po) and mouse (2 mg/kg sc). After iv administration in the rat, the volume of distribution was 1 L/kg and the plasma clearance was 18/mL·min-1·kg-1, giving a 1 h half-life. The volume of distribution is consistent with the physicochemical properties of the compound, and the clearance is in line with estimates from in vitro rat liver microsome (RLM) data (RLM t1/2 >120 min). After oral dosing in the rat, the oral bioavailability was low at 32%.

Solubility

DMSO 69 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light yellow to yellow solid