PFI-1 (PF-6405761)

Catalog No.S1216 Batch:S121601

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Technical Data

Formula

C16H17N3O4S
Molecular Weight 347.39 CAS No. 1403764-72-6
Solubility (25°C)* In vitro DMSO 69 mg/mL (198.62 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description PFI-1 (PF-6405761) is a highly selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC50 of 0.22 μM and for BRD2 with IC50 of 98 nM in a cell-free assay.
Targets
BRD2 [4]
(Cell-free assay)		 BRD4 [1]
(Cell-free assay)
98 nM 0.22 μM
In vitro 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. [1] PFI-1 induces dose-dependent reduction of cell viability in T4302 CD133+ cells. [2] 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). [3]
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. [1]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    T4302 CD133+ cells

  • Concentrations

    1 mM

  • Incubation Time

    5 days

  • Method

    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.
Animal Study:

[1]
  • Animal Models

    Rats

  • Dosages

    1 mg/kg

  • Administration

    Intravenous injection

Selleck's PFI-1 (PF-6405761) has been cited by 11 publications

CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer [ Proc Natl Acad Sci U S A, 2023, 120(4):e2218118120] PubMed: 36652476
Glutathione peroxidase 8 expression on cancer cells and cancer-associated fibroblasts facilitates lung cancer metastasis [ MedComm (2020), 2022, 3(3):e152] PubMed: 35978854
Bromodomain-containing protein 4 (BRD4) as an epigenetic regulator of fatty acid metabolism genes and ferroptosis [ Cell Death Dis, 2022, 13(10):912] PubMed: 36309482
Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection [ Microbiol Spectr, 2022, 10(4):e0241921] PubMed: 35758684
A PGE2-MEF2A axis enables context-dependent control of inflammatory gene expression [ Immunity, 2021, S1074-7613(21)00222-3] PubMed: 34129840
Isoform-specific Involvement of Brpf1 in Expansion of Adult Hematopoietic Stem and Progenitor Cells [ J Mol Cell Biol, 2020, 11;12(5):359-371] PubMed: 31565729
IRF1 Maintains Optimal Constitutive Expression of Antiviral Genes and Regulates the Early Antiviral Response. [ Front Immunol, 2019, 1.1243055556] PubMed: 31156620
The BET-inhibitor PFI-1 diminishes AR/AR-V7 signaling in prostate cancer cells. [ World J Urol, 2019, 37(2):343-349] PubMed: 29934670
A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. [ Nat Commun, 2017, 8:14802] PubMed: 28378740
BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency. [ Sci Rep, 2017, 7(1):16646] PubMed: 29192216

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.