PF-4708671

PF-4708671 is a cell-permeable, highly specific, small molecule inhibitor targeting the kinase activity of **p70 ribosomal S6 kinase 1 (S6K1)**, with a Ki of 20 nM and IC50 of 160 nM[1][3][7]. The drug exhibits approximately 400-fold selectivity over its closely related isoform S6K2 and shows negligible activity against 73 out of 75 tested kinases, with only minimal activity against MSK1 and RSK1 at high concentrations[4][7]. PF-4708671 blocks S6K1-mediated phosphorylation of ribosomal protein S6 while not affecting substrates of related kinases. It also induces phosphorylation of AMPK (AMP-activated protein kinase) independently of S6K1 inhibition by directly inhibiting mitochondrial respiratory chain Complex I[2][5][6]. PF-4708671 has been used widely as an experimental tool to dissect S6K1-dependent cellular mechanisms, elucidate the mTOR/S6K1 pathway’s role in cancer, insulin resistance, and several neurological conditions, and has demonstrated in vitro and in vivo efficacy in modulating cell cycle arrest, protein synthesis, cell proliferation, and tumor growth[1][3][4][5].

Other names

S6K1 inhibitorS-6K1 inhibitorS 6K1 inhibitorp70 Ribosomal S6 Kinase 1 Inhibitorp-70 Ribosomal S6 Kinase 1 Inhibitorp 70 Ribosomal S6 Kinase 1 Inhibitor(2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-5-(trifluoromethyl)-1H-benzo[d]imidazole)