Uses
(S)-PFI-2 is n analog of (R)-PFI-2 a potent and selective lysine methyltransferase SETD7 inhibitor which is a crucial factor in many disease related pathways.
General Description
(S)-PFI-2 is a negative control enantiomer and a biotinylated derivative of (R)-PFI-2, which helps to study the biological activity of SETD7 (SET domain containing (lysine methyltransferase) 7).
Biological Activity
(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].
Biochem/physiol Actions
(S)-PFI-2 is the negative control probe for (R)-PFI-2 hydrochloride, which is a histone-lysine N-methyltransferase (HKMT) inhibitor selective for SETD7 (SET9). (R)-PFI-2 has 1000-fold selectivity for SETD7 (SET9) over other methyltransferases and other non-epigenetic targets and an IC50 value of 2 nM. (S)-PFI-2 is 500-fold less active. For characterization details of (R)-PFI-2 and (S)-PFI-2, please visit the PFI-2 probe summary on the Structural Genomics Consortium (SGC) website.(R)-PFI-2, the active SETD7 probe, is available from Sigma. To learn more about and purchase (R)-PFI-2, click here.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
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.
