PFI-2

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种一流的、有效的、选择性的 SETD7 甲基转移酶抑制剂，Ki app/IC50 为 0.33/2 nM。

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.

(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.

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).

R)-PFI-2

Chromatin/Epigenetic

HMTase

SETD7

Other Indications

——

1627676-59-8

499.5215

C23H25F4N3O3S

>98% (HPLC)

10 mM in DMSO

C1CCN(C1)C(=O)[C@@H](CC2=CC(=CC=C2)C(F)(F)F)NS(=O)(=O)C3=CC(=C4CNCCC4=C3)F

6-Isoquinolinesulfonamide, 8-fluoro-1,2,3,4-tetrahydro-N-[(1R)-2-oxo-2-(1-pyrrolidinyl)-1-[[3-(trifluoromethyl)phenyl]methyl]ethyl]-

(-20℃)

With Ice Pack

≥ 2 years