PFI-2
- Product Name
- PFI-2
- CAS No.
- 1627676-59-8
- Chemical Name
- PFI-2
- Synonyms
- PFI-2;CS-1808;PFI-2 HCl;R-PFI-2 HCl;PFI-2 USP/EP/BP;PFI-2, SETD7 histone lysine methyltransferase inhibitor;8-fluoro-N-[(2R)-1-oxo-1-(pyrrolidin-1-yl)-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide;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
- CBNumber
- CB62729655
- Molecular Formula
- C23H25F4N3O3S
- Formula Weight
- 499.52
- MOL File
- 1627676-59-8.mol
PFI-2 Property
- 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 and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Danger
- Hazard statements
-
H315Causes skin irritation
H318Causes serious eye damage
H411Toxic to aquatic life with long lasting effects
- Precautionary statements
-
P264Wash hands thoroughly after handling.
P264Wash skin thouroughly after handling.
P270Do not eat, drink or smoke when using this product.
P273Avoid release to the environment.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P332+P313IF SKIN irritation occurs: Get medical advice/attention.
P391Collect spillage. Hazardous to the aquatic environment
P501Dispose of contents/container to..…
N-Bromosuccinimide Price
- Product number
- P294055
- Product name
- PFI-2
- Packaging
- 1mg
- Price
- $55
- Updated
- 2021/12/16
- Product number
- orb611667
- Product name
- PFI-2
- Packaging
- 1g
- Price
- $1802
- Updated
- 2021/12/16
- Product number
- B4875
- Product name
- PFI-2
- Packaging
- 25mg
- Price
- $250
- Updated
- 2021/12/16
- Product number
- orb611667
- Product name
- PFI-2
- Packaging
- 100mg
- Price
- $606.9
- Updated
- 2021/12/16
- Product number
- 61050
- Product name
- PFI-2
- Packaging
- 25mg
- Price
- $875
- Updated
- 2021/12/16
PFI-2 Chemical Properties,Usage,Production
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].
in vivo
PFI-2 (i.p., 200 μM, twice a week) attenuates the progression of renal fibrosis and preserves renal function in FA nephropathy[2].
PFI-2 (i.p., 200 μM, twice a week) reduced ECM accumulation and fibroblasts activation after FA injury[2].
PFI-2 (i.p., 200 μM, twice a week) impeded Th2 cytokine signaling activation and M2 macrophage polarization[2].
PFI-2 (i.p., 200 μM, twice a week) suppressed M2 macrophages-myofibroblasts transition and myeloid myofibroblasts accumulation in the FA-treated kidneys[2].
PFI-2 (i.p., 200 μM, twice a week) attenuated macrophages M2 polarization and M2 macrophages-to-myofibroblasts transition in obstructed kidneys[2].
PFI-2 (i.p., 200 μM, twice a week) suppressed myeloid myofibroblast accumulation and renal fibrosis after UUO injury[2].
PFI-2 (i.p., 200 μM, twice a week) reduced the infiltration of inflammatory cells, the production of inflammatory molecules, and NF-κB activation in FA nephropathy.
| Animal Model: | Male C57BL/6 mice (8-10 week old, 20-25 g)[2] |
| Dosage: | 200 μM (PFI-2 is diluted in 100 μL 0.1% (v/v) DMSO to a concentration of 200 μM/100 μL) |
| Administration: | intraperitoneal injection, twice a week |
| Result: | Presented less bone marrow-derived myofibroblasts, fewer CD206+/α-smooth muscle actin + cells and developed less renal fibrosis (P<0.01). Reduced the infiltration of inflammatory cells and decreased the production of pro-inflammatory cytokines and chemokines in the kidneys after folic acid treatment (P<0.01). Suppressed the accumulation of NF-κB p65+ cells in folic acid nephropathy (P<0.01). |
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.
IC 50
SETD7/KMT7
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
Raw materials
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