1255517-76-0

Basic information

• Product Name: 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole
• Synonyms: 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole;PF 4708671;2-[[4-(5-ethyl-4-pyriMidinyl)-1-piperazinyl]Methyl]-6-(trifluoroMethyl)-1H-benziMidazole;PF4708671/PF-4708671;1H-Benzimidazole, 2-[[4-(5-ethyl-4-pyrimidinyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)-;2-[[4-(5-Ethyl-4-pyrimidinyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)-1H-benzimidazole PF-4708671;PF-04708671;2-[[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-6-(trifluoromethyl)-1H-benzimidazole
• CAS NO: 1255517-76-0
• Molecular Formula: C19H21F3N6
• Molecular Weight: 390.4054496
• Product Categories: Amines;Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pfizer Compounds;Pharmaceuticals;PI3K/Akt/mTOR;Akt;mTOR;PI3K
• Mol File: 1255517-76-0.mol
• Article Data: 1

Chemical Properties

• Appearance: off-white/
• Storage Temp.: Store at +4°C
• Solubility: DMSO: ≥20mg/mL
• CAS DataBase Reference: 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole(1255517-76-0)
• EPA Substance Registry System: 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole(1255517-76-0)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1255517-76-0(Hazardous Substances Data)

Usage

Chemical Properties

Pale purple Solid

Uses

PF-4708671 is a highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). PF-4708671 inhibits S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect on highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases.

Biological Activity

pf-4708671 is a cell-permeable and highly specific inhibitor of p70 ribosomal s6 kinase 1 with ic50 value of 160nm [1].s6k1 is a regulator of various biology processes. the inhibition of s6k1 is regard as a therapeutic for the treatment of cancer and insulin resistance. pf-4708671 is the first reported inhibitor of s6k1. it inhibits the activity of s6k1 in the in vitro assay with ki value of 20nm. for the isolated s6k1 from hek293 cell, pf-4708671 shows inhibition with ic50 value of 160nm. the inhibition of s6k1caused by pf-4708671 is much more potent than of other related kinases such as rsk2 and msk1. besides that, pf-4708671 prevents s6k1 from phosphorylating its substrates including the ribosomal s6 protein, mtor and rictor. in addition, pf-4708671 is found to enhance the phosphorylation of s6k1 at thr229 and thr389, results in a subsequent increase of s6k1 activity. whereas this increased activity is much less than that stimulated by igf1 [1].

Biochem/physiol Actions

PF-4708671 is a selective p70 ribosomal S6 kinase (S6K1) inhibitor. PF-4708671 inhibits S6K1 with a Ki of 20 nM and IC50 of 160 nM, while having no effect on the closely related RSK and MSK kinases.

Enzyme inhibitor

This cell-permeable protein kinase inhibitor (FW = 390.41 g/mol; CAS 1255517-76-0; Solubility = 30 mg/mL DMSO, <1 mg/mL H2O) targets p70 ribosomal S6 kinase (S6K1 isoform) with Ki of 20 nM and IC50 of 160 nM, without significant inhibition of S6K2 isoform or Akt1, Akt2, PKA, PKCα, PKC?, PRK2, ROCK2, RSK1, RSK2, or SGK1. PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMAinduced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases.

references

[1] pearce l, alton g, richter d, et al. characterization of pf-4708671, a novel and highly specific inhibitor of p70 ribosomal s6 kinase (s6k1). biochem. j, 2010, 431: 245-255.

Upstream product

• 25198-98-5 5-ethyl-pyrimidin-4-ol 
• 1256492-23-5 5-ethyl-4-(piperazin-1-yl)pyrimidine 
• 107430-29-5 2-(chloromethyl)-5-(trifluoromethyl)-1H-benzo[d]imidazole 

Relevant articles and documents

Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)

S6K1 (p70 ribosomal S6 kinase 1) is activated by insulin and growth factors via the PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin) signalling pathways. S6K1 regulates numerous processes, such as protein synthesis, growth, proliferation and longevity, and its inhibition has been proposed as a strategy for the treatment of cancer and insulin resistance. In the present paperwe describe a novel cell-permeable inhibitor of S6K1, PF-4708671, which specifically inhibits the S6K1 isoform with a Ki of 20 nM and IC50 of 160 nM. PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. PF-4708671 was also found to induce phosphorylation of the T-loop and hydrophobic motif of S6K1, an effect that is dependent upon mTORC1 (mTOR complex 1). PF-4708671 is the first S6K1-specific inhibitor to be reported and will be a useful tool for delineating S6K1-specific roles downstream of mTOR. The Authors.