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Chemical Structure| 1627607-87-7 Chemical Structure| 1627607-87-7

Structure of PFI-2 HCl
CAS No.: 1627607-87-7

Chemical Structure| 1627607-87-7

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PFI-2 HCl is an a first-in-class, potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 with IC50 of 2 nM, 500 fold active than (S)-PFI-2.

Synonyms: (R)-PFI-2 hydrochloride; (R)-PFI-2 (hydrochloride); (-)-PFI-2

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Product Details of PFI-2 HCl

CAS No. :1627607-87-7
Formula : C23H26ClF4N3O3S
M.W : 535.98
SMILES Code : O=S(C1=CC2=C(CNCC2)C(F)=C1)(N[C@H](CC3=CC=CC(C(F)(F)F)=C3)C(N4CCCC4)=O)=O.[H]Cl
Synonyms :
(R)-PFI-2 hydrochloride; (R)-PFI-2 (hydrochloride); (-)-PFI-2
MDL No. :MFCD28133380
InChI Key :ZADKZNVAJGEFLC-ZMBIFBSDSA-N
Pubchem ID :78243738

Safety of PFI-2 HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of PFI-2 HCl

epigenetics

Isoform Comparison

Biological Activity

Description
PFI-2 ((R)-PFI-2 hydrochloride) hydrochloride serves as a highly potent and specific inhibitor of the SET domain-containing lysine methyltransferase 7 (SETD7), with (R)-PFI-2 exhibiting an IC50 value of 2.0 nM, indicating strong inhibitory efficacy, while (S)-PFI-2 displays an IC50 value of 1.0 μM. This compound is utilized in the study of chronic kidney disease and the inflammatory responses that contribute to the development of renal fibrosis.
Target
  • Histone Methyltransferase

    SETD7, IC50:2 nM

    SETD7, Ki:0.33 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
C2C12 cells 4 µM at least 2 hours Inhibition of Setd7 activity to study its effect on β-catenin nuclear accumulation PMC6031334
Primary MuSCs 4 µM 7 days Enhance in vitro expansion of MuSCs and maintain their stemness PMC6031334
J1 mouse embryonic stem cells 5 µM 24 hours Validate the inhibitory effect of (R)-PFI-2 on Set7/9 activity, showing that (R)-PFI-2 effectively reduces Rpl29K5 methylation PMC6102145
NIH 3T3 cells 5 µM 24 hours Validate the inhibitory effect of (R)-PFI-2 on Set7/9 activity, showing that (R)-PFI-2 effectively reduces Rpl29K5 methylation PMC6102145
MCF7 cells 5 μM 1 hour or 5 hours To confirm that ( R)-PFI-2 binds to endogenous human SETD7 in cells, we used structure-guided molecular design to generate PFI-766 (Fig. 4 A), a biotinylated variant of ( R)-PFI-2 that retains the ability to bind and inhibit SETD7 (IC 50110±26 nM in our in vitro enzymatic assay). We used PFI-766 (Fig. 4 A) iμMobilized on streptavidin beads to isolate endogenous SETD7 from lysates of MCF7 cells pretreated (for 1 h or 5 h) with increasing doses of (R)-PFI-2 (Fig. 4 Band C). The amount of SETD7 “pulled down ”by the beads was largely competed off by both 1-h and 5-h pretreatment of live cells with 5 μM(R)-PFI-2. PMC5243171
HEK293 cells 10 μM Cellular thermal shift assay (CETSA) that measures ligand-induced stabilization of a target protein in cells showed a 4 °C increase in the apparent thermal stability of Flag-tagged SETD7 in HEK293 cells at 10 μM(R)-PFI-2, indicating that ( R)-PFI-2 passed through the cell membrane and bound to and stabilized SETD7 ( SI Appendix , Fig. S4 Cand D). PMC10549198

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice mdx-NSG mice Transplantation after in vitro culture 3 mg/kg Once daily for 5 consecutive days, repeated every 2 weeks, for 55 days Enhance engraftment and therapeutic efficacy of MuSCs PMC6031334

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.87mL

0.37mL

0.19mL

9.33mL

1.87mL

0.93mL

18.66mL

3.73mL

1.87mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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