| Identification | Back Directory | [Name]
PFI-2 | [CAS]
1627676-59-8 | [Synonyms]
PFI-2
CS-1808
PFI-2 HCl
R-PFI-2 HCl
PFI-2 USP/EP/BP
8-fluoro-1,2,3,4-tetrahydro-N-[(1R)-2-oxo-2-(1-pyrrolidinyl)-1-[[3-(trifluoromethyl)phenyl]methyl]ethyl]-6-isoquinolinesulfonamide
6-Isoquinolinesulfonamide, 8-fluoro-1,2,3,4-tetrahydro-N-[(1R)-2-oxo-2-(1-pyrrolidinyl)-1-[[3-(trifluoromethyl)phenyl]methyl]ethyl]-
(R)-8-fluoro-N-(1-oxo-1-(pyrrolidin-1-yl)-3-(3-(trifluoromethyl)phenyl)propan-2-yl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (R)-PFI 2 hydrochloride | [Molecular Formula]
C23H25F4N3O3S | [MDL Number]
MFCD28348361 | [MOL File]
1627676-59-8.mol | [Molecular Weight]
499.52 |
| Chemical Properties | Back Directory | [Boiling point ]
642.7±65.0 °C(Predicted) | [density ]
1.371±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥50 mg/mL in DMSO; ≥1.51 mg/mL in H2O with gentle warming and ultrasonic; ≥8.12 mg/mL in EtOH | [form ]
solid | [pka]
8.95±0.20(Predicted) |
| Hazard Information | Back Directory | [Uses]
PFI-2 is a potent and selective lysine methyltransferase SETD7 inhibitor which is a crucial factor in many disease related pathways. | [Biological Activity]
pfi-2 is a potent and selective inhibitor of setd7 methyltransferase with ic50 value of 2.0 nm [1].set domain containing (lysine methyltransferase) 7 (setd7) is a protein lysine methyltransferase that acts as monomethyltransferase of lysine 4 on histone h3 (h3k4) and regulates dna methyltransferase 1 (dnmt1) [1].pfi-2 is a potent and selective setd7 methyltransferase inhibitor. (r)-pfi-2 inhibited human setd7 methyltransferase activity with ic50 value of 2.0 nm. however, (s)-pfi-2 was 500-fold less active with ic50 value of only 1.0 μm. (r)-pfi-2 potently inhibited setd7 with morrison kiapp value of 0.33 nm. (r)-pfi-2 occupied the peptide binding groove and effectively inhibited the binding of setd7 substrates. in the presence of 20 μm sam, (r)-pfi-2 bound to setd7 with kd value of 4.2 nm in a sam-dependent way. in hek293 cells, (r)-pfi-2 (10 μm) bound to and stabilized setd7. in setd7+/+ murine embryonic fibroblasts (mefs), (r)-pfi-2 increased nuclear localization of yes-associated protein (yap) and the expression of yap target genes ctgf, gli2 and cdc20 [1]. | [Enzyme inhibitor]
This SETD7 inhibitor (FW = 499.52 g/mol; CAS 1627676-59-8; IUPAC: 8-
fluoro-1,2,3,4-tetrahydro-N-[ (1R) -2-oxo-2- (1-pyrrolidinyl) -1-[[3-
(trifluoromethyl) phenyl]methyl]ethyl]-6-isoquinolinesulfonamide, targets
the SET domain containing lysine methyltransferase, or SETD7 (Ki = 0.33
nM; IC50 = 2 nM), showing 1000-times selectivity versus other methyl-
transferases and other non-epigenetic targets. (R) -PFI-2 exhibits an unusual
cofactor-dependent and substrate-competitive inhibitory mechanism by
occupying the substrate peptide binding groove of SETD7, including the
catalytic lysine-binding channel, and by making direct contact with the
donor methyl group of the cofactor, S-adenosylmethionine. In murine
embryonic fibroblasts, (R) -PFI-2 treatment phenocopies the effects of Setd7
deficiency on Hippo pathway signaling, via modulation of the
transcriptional coactivator Yes-associated protein (YAP) and regulation of
YAP target genes. In confluent MCF7 cells, (R) -PFI-2 rapidly alters YAP
localization, suggesting continuous and dynamic regulation of YAP by the
methyltransferase activity of SETD7. | [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, 111(35): 12853-12858. |
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