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| Product Name: | PFI-2 | | Synonyms: | (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;PFI-2 HCl;8-fluoro-1,2,3,4-tetrahydro-N-[(1R)-2-oxo-2-(1-pyrrolidinyl)-1-[[3-(trifluoromethyl)phenyl]methyl]ethyl]-6-isoquinolinesulfonamide;PFI-2;R-PFI-2 HCl;CS-1808;6-Isoquinolinesulfonamide, 8-fluoro-1,2,3,4-tetrahydro-N-[(1R)-2-oxo-2-(1-pyrrolidinyl)-1-[[3-(trifluoromethyl)phenyl]methyl]ethyl]-;PFI-2 USP/EP/BP | | CAS: | 1627676-59-8 | | MF: | C23H25F4N3O3S | | MW: | 499.52 | | EINECS: | | | Product Categories: | Inhibitors | | Mol File: | 1627676-59-8.mol |  |
| | PFI-2 Chemical Properties |
| 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) |
| | PFI-2 Usage And Synthesis |
| 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 methyltransferases 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. |
| | PFI-2 Preparation Products And Raw materials |
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