(S)-PFI-2 (hydrochloride) is the inactive enantiomer of (R)-PFI-2 and may serve as a negative control. (R)-PFI-2 is a cell-permeable and potent SET7/9 inhibitor with IC50 value of 2 nM [1].
Protein methyltransferases involve in the epigenetic regulation of gene transcription, silencing, chromatin structure establishment, maintenance, DNA repair, and replication. SET domain containing (lysine methyltransferase) 7 (SETD7) (SET9; SET7/9, KMT7) is a protein lysine methyltransferases and is originally characterized as a monomethyltransferase of lysine 4 on histone H3 (H3K4me1). SET7/9 has very broad target specificity that methylates histone H3, tumor suppressor p53 and transcription factor TAF10 [1][2][3].
(S)-PFI-2 (hydrochloride), the inactive enantiomer of (R)-PFI-2, was 500-fold less potent with IC50 value of 1 μM and used as a negative control in chemical biology experiments. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase with IC50 value of 2 nM. In high-density MCF7 cells, (R)-PFI-2 dose-dependently increased nuclear YAP and enhanced expression of the YAP target genes AREG and CYR61, whereas (S)-PFI-2 had no effect [1].
References:
[1]. Barsyte-Lovejoy D, Li F, Oudhoff MJ, et al. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12853-8.
[2]. Kurash JK, Lei H, Shen Q, et al. Methylation of p53 by Set7/9 mediates p53 acetylation and activity in vivo. Mol Cell. 2008 Feb 15;29(3):392-400.
[3]. Couture JF, Collazo E, Hauk G, et al. Structural basis for the methylation site specificity of SET7/9. Nat Struct Mol Biol. 2006 Feb;13(2):140-6.