PFI-2

SKU: orb1226028

Description

A first-in-class, potent and selective inhibitor of SETD7 methyltransferase with Ki app/IC50 of 0.33/2 nM; shows high selectivity (>1,000-fold) for SETD7 over 18 other methyltransferases and DNMT1, 500-fold more active than enantiomer (S)-PFI-2; increases YAP nuclear localization, regulates YAP target genes, and phenocopys the effects of Setd7 deficiency on Hippo pathway signaling in murine embryonic fibroblasts.

Key Properties

• CAS Number: 1627676-59-8
• MW: 499.5215
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₅F₄N₃O₃S
• SMILES: C1CCN(C1)C(=O)[C@@H](CC2=CC(=CC=C2)C(F)(F)F)NS(=O)(=O)C3=CC(=C4CNCCC4=C3)F
• Target: HMTase
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  PFI-2 (i.p. , 200 μM, twice a week) attenuates the progression of renal fibrosis and preserves renal function in FA nephropathy. PFI-2 (i.p. , 200 μM, twice a week) reduced ECM accumulation and fibroblasts activation after FA injury. PFI-2 (i.p. , 200 μM, twice a week) impeded Th2 cytokine signaling activation and M2 macrophage polarization. PFI-2 (i.p. , 200 μM, twice a week) suppressed M2 macrophages-myofibroblasts transition and myeloid myofibroblasts accumulation in the FA-treated kidneys. PFI-2 (i.p. , 200 μM, twice a week) attenuated macrophages M2 polarization and M2 macrophages-to-myofibroblasts transition in obstructed kidneys. PFI-2 (i.p. , 200 μM, twice a week) suppressed myeloid myofibroblast accumulation and renal fibrosis after UUO injury. 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). 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).
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• In Vitro:
  (R)-PFI-2 shows high inhibiting activity with IC50 value of 2.0 nM and (S)-PFI-2 shows inhibiting activity with IC50 value of 1.0 μM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

R)-PFI-2

Quick Database Links

Gene Symbol

HMTase