PFI-1 --- BET Inhibitor

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.

Product information

CAS Number: 1403764-72-6

Molecular Weight: 347.39

Formula: C16H17N3O4S

Chemical Name: 2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide

Smiles: COC1=CC=CC=C1S(=O)(=O)NC1=CC2CN(C)C(=O)NC=2C=C1

InChiKey: TXZPMHLMPKIUGK-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

PFI-1 was used at 10 µM final concentration in various in vitro assays.

In Vivo:

PFI-1 could be dosed to rats by IV administration at 1 mg/kg once per day, or oral administration at 2 mg/kg once per day.

References:

1. Fish PV, et al. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. (2012) J Med Chem. 55(22):9831-7.
2. Picaud S, et al. PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains. (2013) Cancer Res. 73(11):3336-3346.

Products are for research use only. Not for human use.

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