PF-4708671

Description: PF-4708671 is a novel, potent, highly specific and cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform)/RSK1 with potential antitumor activity. It inhibits RSK1 with a Ki/IC50 of 20 nM/160 nM in cell-free assays, exhibits 400-fold greater selectivity for S6K1 over S6K2, and displays 4- and > 20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. As the first S6K1-specific inhibitor reported, PF-4708671 showed potent antiproliferative activity in vitro and high antitumor efficacy in vivo by preventing 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.

References:Biochem J. 2010 Oct 15; 431(2):245-55.