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Description: PFI-1 (PF6405761) is a novel, highly potent and selective BET (bromodomain-containing protein) inhibitor with antineoplastic activity. It inhibits BRD4 with an 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. PFI-1 has antiproliferative effects on leukaemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell cycle arrest, down-regulation of MYC expression as well as induction of apoptosis and induces differentiation of primary leukaemic blasts.
References: J Med Chem. 2012 Nov 26;55(22):9831-7; Clin Cancer Res. 2013 Apr 1;19(7):1748-59.
Chemical Name: 2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide
InChi Key: TXZPMHLMPKIUGK-UHFFFAOYSA-N
InChi Code: InChI=1S/C16H17N3O4S/c1-19-10-11-9-12(7-8-13(11)17-16(19)20)18-24(21,22)15-6-4-3-5-14(15)23-2/h3-9,18H,10H2,1-2H3,(H,17,20)
SMILES Code: O=S(C1=CC=CC=C1OC)(NC2=CC3=C(NC(N(C)C3)=O)C=C2)=O
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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: PFI-1 is a selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC50 of 0.22 μM in a cell-free 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.
J Med Chem. 2012 Nov 26;55(22):9831-7; Clin Cancer Res. 2013 Apr 1;19(7):1748-59.
Purity ≥98%
COA
MSDS