PFI-1

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Chemical Structure| 1403764-72-6 同义名 : PF-06405761; PF-6405761
CAS号 : 1403764-72-6
货号 : A280183
分子式 : C16H17N3O4S
纯度 : 98%
分子量 : 347.39
MDL号 : MFCD22580416
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(100.75 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • BET

    BRD2, IC50:98 nM

    BRD4, IC50:0.22 μM
描述 PFI-1 is a potent and selective BET inhibitor with IC50 value of 0.22μM for BRD4(1). PFI-1 exhibited inhibitory effect on IL6 production from human blood mononuclear cells stimulated by LPS with EC50 value of 1.89μM[3]. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth with GI50 values ranging in 0.8-11μM. Exposure of sensitive cell lines with PFI-1 resulted in G1 cell cycle arrest, downregulation of MYC expression in MV4;11 cells, as well as induction of apoptosis and induced differentiation of primary leukemic blasts. Cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10[4].
作用机制 PFI-1 could bind to BET protein through the key interaction with Asn140. And the urea carbonyl also makes a water-bridged hydrogenbond interaction with the phenolic OH of Tyr97[3]. PFI-1 efficiently blocks the interaction of BET BRDs with acetylated histone tails. It acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2.[4]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.88mL

0.58mL

0.29mL

14.39mL

2.88mL

1.44mL

28.79mL

5.76mL

2.88mL
参考文献

[1]Fish PV, Filippakopoulos P, et al. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7.

[2]Picaud S, Da Costa D, et al. PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res. 2013 Jun 1;73(11):3336-46.

[3]Fish PV, Filippakopoulos P, Bish G, Brennan PE, Bunnage ME, Cook AS, Federov O, Gerstenberger BS, Jones H, Knapp S, Marsden B, Nocka K, Owen DR, Philpott M, Picaud S, Primiano MJ, Ralph MJ, Sciammetta N, Trzupek JD. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem. 2012 Nov 26;55(22):9831-7. doi: 10.1021/jm3010515. Epub 2012 Nov 8. PMID: 23095041; PMCID: PMC3506127.

[4]Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O'Sullivan B, Müller S, Schwaller J, Stankovic T, Knapp S. PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res. 2013 Jun 1;73(11):3336-46. doi: 10.1158/0008-5472.CAN-12-3292. Epub 2013 Apr 10. PMID: 23576556; PMCID: PMC3673830.