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Chemical Structure| 1255517-76-0 Chemical Structure| 1255517-76-0

Structure of PF-4708671
CAS No.: 1255517-76-0

Chemical Structure| 1255517-76-0

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PF-4708671 is a potent, cell-permeable S6K1 inhibitor with a Ki of 20 nM and an IC50 of 160 nM.

Synonyms: PF-04708671

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Product Details of PF-4708671

CAS No. :1255517-76-0
Formula : C19H21F3N6
M.W : 390.41
SMILES Code : FC(C1=CC=C2C(NC(CN3CCN(C4=NC=NC=C4CC)CC3)=N2)=C1)(F)F
Synonyms :
PF-04708671
MDL No. :MFCD18086922
InChI Key :FBLPQCAQRNSVHB-UHFFFAOYSA-N
Pubchem ID :51371303

Safety of PF-4708671

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

Related Pathways of PF-4708671

MAPK
PI3K-AKT

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
LS174T cells 10 µM 24 hours PF-4708671 significantly increased either mitomycin C or the combination-induced apoptosis (PARP cleavage, hallmark of apoptosis), indicating S6K1 negatively regulated the combination treatment-induced apoptosis and S6K1 inactivation in the combination treatment contributed to the induction of apoptosis. PMC6289385
mouse neural progenitor cells 10 μM 1 hour to 15 hours PF-4708671 rescued the migration defect caused by STRADA knockdown by inhibiting p70S6K, indicating that STRADA regulates cell migration through the mTORC1/p70S6K signaling pathway. PMC3720125
hippocampal slices 10 μM Measure phosphorylation of the S6K1 substrate ribosomal protein S6 to determine the optimal concentration of PF-4708671 PMC4908636
cortical lysates 10 μM 15 minutes Measure protein synthesis rates, finding that PF-4708671 significantly reduced protein synthesis in FXS model mice PMC4908636
HCT116 cells 10 μmol/L 72 hours To evaluate the inhibitory effect of PF-4708671 in combination with OSI-906 on the proliferation of HCT116 cells. The results showed that the combination significantly inhibited cell proliferation. PMC4456303
SW480 cells 10 μmol/L 72 hours To evaluate the inhibitory effect of PF-4708671 in combination with OSI-906 on the proliferation of SW480 cells. The results showed that the combination significantly inhibited cell proliferation. PMC4456303
HGUE-C-1 30 μM 24 hours PF-4708671 suppressed the phosphorylation of RPS6 and resensitized cells to Selumetinib. PMC4212257
DLD-1 30 μM 24 hours PF-4708671 suppressed the phosphorylation of RPS6 and resensitized cells to Selumetinib. PMC4212257
HCT-15 30 μM 24 hours PF-4708671 suppressed the phosphorylation of RPS6 and resensitized cells to Selumetinib. PMC4212257
SW480 30 μM 24 hours PF-4708671 suppressed the phosphorylation of RPS6 and resensitized cells to Selumetinib. PMC4212257
NSC34 cells 5 µM, 10 µM, 20 µM 16 hours To study the effect of PF-4708671 on autophagy, the results showed that PF-4708671 increased LC3-II lipidation, indicating autophagy was induced. PMC5851998
PC-9/G cells 4 μM 24 hours PF-4708671 effectively inhibited S6K1 activity in PC-9/G cells. PMC7718330
HCC827-OR cells 2 μM, 4 μM 24 hours PF-4708671 synergistically enhanced the cytotoxicity of osimertinib in HCC827-OR cells. PMC7718330
μM1.s 10 µM 48 hours S6K1i inhibits S6 phosphorylation and synergizes with MCL-1i to induce apoptosis in μM1.s cells PMC8270664
OPM-2 10 µM 48 hours S6K1i inhibits S6 phosphorylation and synergizes with MCL-1i to induce apoptosis in OPM-2 cells PMC8270664
L363 10 µM 48 hours S6K1i inhibits S6 phosphorylation and synergizes with MCL-1i to induce apoptosis in L363 cells PMC8270664

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
mice Fmr1 knockout mice intraperitoneal injection 0.1 mg/kg Single injection Evaluate the effects of PF-4708671 on protein synthesis and behavioral phenotypes in FXS model mice, finding it significantly reduced eEF2 phosphorylation and reversed social behavior deficits and behavioral inflexibility PMC4908636
nude mice HCT116 xenograft model orally 1 mg/mL, 200 µL every three days for 15 days To evaluate the inhibitory effect of PF-4708671 in combination with OSI-906 on HCT116 xenograft tumors. The results showed that the combination significantly inhibited tumor growth. PMC4456303
C57BL/6 mice Adult wild type mice Intraperitoneal injection 25 mg/kg daily for 10 days To investigate the effect of PF-4708671 on offline motor learning gains, results showed that PF-4708671 inhibited offline motor learning gains. PMC7315768
nude mice subcutaneous xenograft model intraperitoneal injection 60 mg/kg once every other day for 15 days PF-4708671 significantly reduced tumor volume and weight when combined with osimertinib, without causing severe side effects. PMC7718330

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.56mL

0.51mL

0.26mL

12.81mL

2.56mL

1.28mL

25.61mL

5.12mL

2.56mL

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

References

 

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