PFI-1 (PF-6405761)

製品コードS1216 バッチS121651

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C16H17N3O4S
分子量 347.39 CAS No. 1403764-72-6
Solubility (25°C)* 体外 DMSO 69 mg/mL (198.62 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 PFI-1 (PF-6405761)は、高選択的なBET (ブロモドメイン含有タンパク質)阻害剤であり、セルフリーアッセイにおいてBRD4に対するIC50は0.22 μM、BRD2に対するIC50は98 nMです。
in vitro PFI-1 (PF-6405761) binds to cyclic AMP response binding protein with KD of 49 μM and has an EC50 of 1.89 μM for the inhibition of IL6 production from human blood mononuclear cells stimulated by LPS. It induces dose-dependent reduction of cell viability in T4302 CD133+ cells. This compound also inhibits the proliferation of three NET cell lines (Bon-1 derived from a pancreatic NET, and H727 and H720 derived from lung NETs).
in vivo S1216 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. S1216 oral dosed (2 mg/kg) in the rat results in the oral bioavailability as low as 32%. S1216 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.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 T4302 CD133+ cells
濃度 1 mM
反応時間 5 days
実験の流れ

To determine dose response for PFI-1 (PF-6405761), cells are aliquoted into 96-well plate at 5 × 103 cells per well in triplicates. This compound 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.
動物実験 動物モデル Rats
投薬量 1 mg/kg
投与方法 Intravenous injection

参考

  • https://pubmed.ncbi.nlm.nih.gov/23095041/
  • https://pubmed.ncbi.nlm.nih.gov/23403638/
  • http://www.endocrine-abstracts.org/ea/0031/ea0031P149.htm
  • https://pubmed.ncbi.nlm.nih.gov/23576556/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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