Description
PFI 4 is an SGC chemical probe for the bromodomains of the BRPF (BRomodomain and PHD Finger containing) scaffolding protein BRPF1B. PFI 4 specifically binds to BRPF1B with an IC50 = 172 nM and Kd =13 nM as determined by ITC. PFI 4 reduces recovery time in triple BRD cell construct in FRAP and is potent in cells with IC50 250nM, while showing no effect on BRPF1A. PFI 4 exhibits >100-fold selectivity for BRPF1 over a panel of other bromodomains including BRPF2 (BRD1), BRPF3 and BRD4.
Uses
PFI-4 is a chemical probe that specifically binds to the bromodomain of BRPF1 inhibiting binding to tri-acetylated histone 4 affecting the development of multiple tissues axial skeleton and hematopoietic system.
Biological Activity
pfi 4 is a cell permeable, potent and selective inhibitor of brpf1 bromodomain with pic50 and pkd values of 7.1 and 8.0 [1].the brpf (bromodomain and phd finger-containing) family brpf1, brpf2/brd1, and brpf3 operate as scaffolds to assemble myst-family histone acetyltransferases (hats) complexes. brpf1 is a component of complexes containing the moz/morf transcriptional coactivators and links the catalytic hats to the other subunits ing5 and heaf6.8. brpf1 is important for maintaining skeletal development and hox gene expression in fish [1].in the bromoscan panel of 35 bromodomain binding assays, pfi 4 exhibited excellent brpf1 potency with pkd value of 8.0 and excellent selectivity over other bromodomains. in a cellular protein interaction assay, pfi 4 displaced nanoluc-tagged brpf1 bromodomain from halotaggedhistone h3.3 and disrupted chromatin binding [1].
Biochem/physiol Actions
PFI-4 is an SGC chemical probe for the bromodomains of the BRPF (BRomodomain and PHD Finger containing) scaffolding protein BRPF1B. The BRPF proteins (BRPF1/2/3) assemble histone acetyltransferase (HAT) complexes of the MYST transcriptional coactivator family members MOZ and MORF. The BRPF1 protein is the scaffold subunit of the MYST acetyltransferase complex, which plays a crucial roles in DNA repair, recombination and replication as well as transcription activation. Mutations in MOZ, MORF, and BRPF1 have all been associated with cancer. BRPF1 exists in 2 different isoforms: BRPF1A and BRPF1B. PFI-4 specifically binds 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 250nM, while showing no effect on BRPF1A. For full characterization details, please visit the PFI-4 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
References
[1]. demont eh, bamborough p, chung cw, et al. 1,3-dimethyl benzimidazolones are potent, selective inhibitors of the brpf1 bromodomain. acs med chem lett, 2014, 5(11): 1190-1195.
