1819363-80-8

Basic information

• Product Name: PFI3
• Synonyms: PFI3;PFI-3;(E)-1-(2-Hydroxyphenyl)-3-((1R,4R)-5-(pyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one;(2E)-1-(2-Hydroxyphenyl)-3-[(1R,4R)-5-(2-pyridinyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-2-propen-1-one
• CAS NO: 1819363-80-8
• Molecular Formula: C19H19N3O2
• Molecular Weight: 321.37306
• Product Categories: Inhibitors
• Mol File: 1819363-80-8.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (>25 mg/ml)
• Stability: Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: PFI3(CAS DataBase Reference)
• NIST Chemistry Reference: PFI3(1819363-80-8)
• EPA Substance Registry System: PFI3(1819363-80-8)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 1819363-80-8(Hazardous Substances Data)

Usage

Description

PFI-3, with the chemical formula (1819363-80-8), is a selective inhibitor that targets family VIII bromodomains, specifically PB1(5), SMARCA2, and SMARCA4. It exhibits complete selectivity over all non-family VIII bromodomains. PFI-3 has been shown to block adipogenesis in C3H10T1/2 mesenchymal cells at a concentration of 20μM. Additionally, when embryonic stem cells are treated with PFI-3, it leads to the deprivation of stemness and deregulated lineage specificity. Furthermore, the presence of PFI-3 enhances the differentiation of trophoblast stem cells. PFI-3 is a cell-permeable compound.

Uses

Used in Cancer Research and Treatment:
PFI-3 is used as a selective chemical inhibitor for SMARCA (2/4) and PBI (5) bromodomains, which may contribute to the delay and prevention of breast cancer. By targeting these specific bromodomains, PFI-3 has the potential to disrupt cancer-related pathways and inhibit tumor growth.
Used in Stem Cell Research:
In the field of stem cell research, PFI-3 is used to study the effects of bromodomain inhibition on stem cell stemness and lineage specificity. Treatment with PFI-3 has been shown to lead to the deprivation of stemness and deregulated lineage specificity in embryonic stem cells, making it a valuable tool for understanding the molecular mechanisms underlying stem cell differentiation and pluripotency.
Used in Trophoblast Stem Cell Differentiation:
PFI-3 is also used to enhance the differentiation of trophoblast stem cells. Its presence during the differentiation process has been shown to improve the efficiency and specificity of this process, which could have implications for understanding and treating conditions related to trophoblast development and function.
Used in Drug Development:
As a selective inhibitor of specific bromodomains, PFI-3 can be utilized in the development of novel therapeutics targeting cancer and other diseases associated with the dysregulation of these bromodomain proteins. Its cell-permeable nature makes it a promising candidate for the development of drugs that can effectively penetrate cell membranes and reach their target proteins within the cell.

Biochem/physiol Actions

SMARCA4 (SWI/SNF related, Matrix associated, Actin dependent Regulator of Chromatin, subfamily A, member 4) is a transcriptional activator and is a component of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. SMARC4 (also known as BRG1) and the related protein SMARCA2 (also known as BRM) contain a bromodomain that is structurally similar to the PolyBromo1 (PB1) 5 bromodomain. PFI-3 is a selective chemical probe for SMARCA bromodomains that inhibits SMARCA2, SMARCA4 and PB1(5) bromodomains. For full characterization details, please visit the PFI-3 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

References

Gerstenberger et al. (2016), Identification of a chemical probe for family VIII bromodomains through optimization of a fragment hit; J. Med. Chem. 59 4800 Fedorov et al. (2015), Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance; Sci. Adv. 1 e1500723

Upstream product

• 39079-62-4 chromone-3-carboxylic acid 
• 109-04-6 2-bromo-pyridine 
• 134003-84-2 tert-butyl (1R,4R)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate 

Relevant articles and documents

Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit

The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays.

BROMODOMAIN INHIBITORS TO TARGET THERAPY-RESISTANT CANCER

Novel inhibitors of the bromodomain of Brahma-related gene 1 (BRG1) are described. Also described are methods of treating glioblastoma using inhibitors of the BRG1 bromodomain in combination with chemotherapeutics, such as DNA alkylating agents. As described herein, the inhibitors sensitize glioblastoma cells, including chemoresistant glioblastoma cells, to DNA alkylating agents, for example, temozolomide and carmustine.