PFI-2
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].
Reference:
[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.
- 1. Chi Hin Wong, Chi Han Li, et al. "The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer." bioRxiv. 2019 October 21.
- 2. Li N, Yang L, et al. "BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc." Cell Death Dis. 2018 Jul 9;9(7):761. PMID:29988031
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 499.52 |
| Cas No. | 1627676-59-8 |
| Formula | C23H25F4N3O3S |
| Solubility | ≥50 mg/mL in DMSO; ≥1.51 mg/mL in H2O with gentle warming and ultrasonic; ≥8.12 mg/mL in EtOH |
| Chemical Name | 8-fluoro-N-[(2R)-1-oxo-1-pyrrolidin-1-yl-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide |
| SDF | Download SDF |
| Canonical SMILES | C1CCN(C1)C(=O)C(CC2=CC(=CC=C2)C(F)(F)F)NS(=O)(=O)C3=CC(=C4CNCCC4=C3)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Methyltransferase activity |
Recombinant human SETD7 (residues 1–366) and SET domain only (residues109–366) were expressed in Escherichia coli and purified to homogeneity. Methyltransferase activity of SETD7(1-366) was assayed using a scintillation proximity assay monitoring the incorporation of the tritium-labeled methyl group of 3H-SAM into a peptide substrate corresponding to histone H3 residues 1-25 at 2 μM SAM and 2 μM H3(1–25) and 2 nM enzyme. |
| Cell experiment [1]: | |
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Cell lines |
MEFs and MCF7 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0-10 μM, 2h |
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Applications |
In Setd7+/+ murine embryonic fibroblasts (MEFs) in the presence of (R)-PFI-2 (10 μM), Setd7+/+ MEFs grown to confluence and displayed increased nuclear localization of YAP, as well as increased expression of YAP-dependent genes Ctgf, Gli2, and Cdc20. (R)-PFI-2 had no effect in Setd7-/- MEFs. In confluent MCF7 cells, (R)-PFI-2 (1 μM for 2h) dose-dependently increased nuclear YAP and increased expression of the YAP target genes AREG and CYR61. |
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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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Quality Control & MSDS
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Chemical structure
Related Biological Data
