product name PFI-1 (PF-6405761)
Description: PFI-1 is a highly potent and selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC50 of 0.22 μM in cell-free assays. Co-crystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukaemic cell lines and efficiently abrogates their clonogenic growth.
References: J Med Chem. 2012 Nov 26;55(22):9831-7; Clin Cancer Res. 2013 Apr 1;19(7):1748-59.
347.39
Formula
C16H17N3O4S
CAS No.
1403764-72-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 69 mg/mL (198.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19419454
| In Vitro |
In vitro activity: PFI-1 binds to with cyclic AMP response binding protein with KD of 49 μM. PFI-1 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. PFI-1 inhibits the proliferating of three NET cell lines (Bon-1 derived from a pancreatic NET, and H727 and H720 derived from lung NETs). Kinase Assay: Cell Assay: To determine dose response, cells are aliquoted into 96-well plate at 5 × 103 cells per well in triplicates. PFI-1 is added by 2- or 4-fold serial dilutions. Cell number is measured 5 days after plating using the CellTiter-Glo Kit and normalized to corresponding vehicle-treated groups. IC50 values are calculated by the GraphPad Prism 5 software using the 4-parameter logistic nonlinear regression model. To calculate the relative growth of cells, averaged cell titers of each group on day 1 are assigned a value of 1. All subsequent cell titer values are normalized accordingly. |
|---|---|
| In Vivo | PFI-1 administrated (1 mg/kg i.v.) in the rat results in the volume of distribution of 1 L/kg, the plasma clearance of 18/mL·min–1·kg–1 and half-life of 1 hour. PFI-1 oral dosed (2 mg/kg) in the rat results in the oral bioavailability as low as 32%. PFI-1 administrated (2 mg/kg s.c.) in the mouse results in a Cmax of 58 ng/mL with a Tmax of 1 h and a half-life of approximately 2 hours. |
| Animal model | Rats model |
| Formulation & Dosage | Dissolved in normal saline; 1mg/kg; i.v. injection |
| References | J Med Chem. 2012 Nov 26;55(22):9831-7; Clin Cancer Res. 2013 Apr 1;19(7):1748-59. |
