(R)PFI-2 HCl

Biological Activity

PFI-2 hydrochloride is a a first-in-class, potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 with IC50 of 2 nM, 500 fold active than (S)-PFI-2.(R)-PFI-2 is highly selective (>1,000-fold) for SETD7, over a panel of 18 other human protein methyltransferases and DNMT1, and was shown to be inactive against 134 additional ion channel, GPCR, and enzyme targets (<35% inhibition at 10 μM). (R)-PFI-2 binds to SETD7 only in the presence of SAM. PFI-766, a biotinylated variant of (R)-PFI-2 that retains the ability to bind and inhibit SETD7 (IC50 110 ± 26 nM in our in vitro enzymatic assay). PFI-766 engagement of endogenous SETD7 was also confirmed by mass spectrometry that supported the high specificity of the compound for endogenous SETD7.

Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.