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.
