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Description: PFI-4 is a novel, potent, cell permeable and selective inhibitor of bromodomain and PHD finger-containing protein 1 (BRPF1) with antineoplastic activity. It inhibits BRPF1 with an IC50 of 80 nM. PFI-4 aacts by specifically binding to BRPF1B with a Kd =13 nM as determined by ITC. It reduces recovery time in triple BRD cell construct in FRAP and is potent in cells with IC50 of 250nM, while showing no effect on BRPF1A. BRPF1A may act as dominant negative isoform of BRPF1 generated by alternative splicing. BRPF1 exists in 2 different isoforms: BRPF1A and BRPF1B. A residue insertion in the ZA loop of BRPF1A prevents binding to acetylated histone peptides. BRPF1A may act as dominant negative isoform of BRPF1 generated by alternative splicing.
References: ACS Med Chem Lett. 2014 Sep 10;5(11):1190-5.
Chemical Name: N-[2,3-Dihydro-1,3-dimethyl-2-oxo-6-(1-pyrrolidinyl)-1H-benzimidazol-5-yl]-2-methoxybenzamide
InChi Key: QCIJLRJBZDBVDB-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H24N4O3/c1-23-17-12-15(22-20(26)14-8-4-5-9-19(14)28-3)16(25-10-6-7-11-25)13-18(17)24(2)21(23)27/h4-5,8-9,12-13H,6-7,10-11H2,1-3H3,(H,22,26)
SMILES Code: O=C(NC1=C(N2CCCC2)C=C(N3C)C(N(C)C3=O)=C1)C4=CC=CC=C4OC
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: PFI-4 is cell permeable, and acts by displacing the BRPF1 bromodomain from Histone H3.3.
Kinase Assay: PFI-4 is a potent and selective and cell permeable BRPF1 bromodomain inhibitor (IC50 = 80 nM). Exhibits >100-fold selectivity for BRPF1 over a panel of other bromodomains including BRPF2 (BRD1), BRPF3 and BRD4.
Cell Assay: Disrupts BRPF1 binding to histone H3.3. PFI-4 is a chemical probe that specifically binds to the bromodomain of BRPF1 with a Kd =13 nM as determined by ITC. It reduces recovery time in triple BRD cell construct in FRAP, inhibiting binding to tri-acetylated histone 4 (residues 1-21). It has much lower affinity for bromodomain 1 of BRD4 (Kd = >50 μM) and is selective for BRPF1 over BRPF2 and BRPF3. PFI-4 is potent in cells, with an IC50 value of 250 nM.
ACS Med Chem Lett. 2014 Sep 10;5(11):1190-5
Purity ≥98%
COA
MSDS
NMR