PF-4708671是一种细胞渗透性p70 ribosomal S6 kinase(S6K1亚型)抑制剂，在无细胞试验中Ki/IC50为20 nM/160 nM，作用于S6K1比作用于S6K2选择性高400倍，作用于S6K1比作用于MSK1和RSK1/2选择性分别高4和20倍以上，是第一个报道的S6K1特异性抑制剂。

≥98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

PF 4708671; PF4708671

Off-white Powder

DMSO ：30 mg/mL (76.84 mM)
Ethanol ：8 mg/mL (20.49 mM)

Ribosomal S6 Kinase (RSK)

PF-4708671 is a piperazinyl-pyrimidine analogue and the first S6K1-specific inhibitor. PF-4708671 does not significantly inhibit the activity of the closely related S6K2 isoform or a number of other AGC kinases (Akt1, Akt2, PKA, PKCα, PKCϵ, 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 PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. PF-4708671 is 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 does not affect activity of mTORC1.

The tumor growth rate in mice treated with the combination of OSI-906+PF-4708671 is significantly slower than that of OSI-906 alone (P=0.0189) or PF4708671 alone (P=0.0165) treated mice. The average tumor volume in the OSI-906+PF-4708671-treated mice is approximately 50% of that in mice treated with OSI-906 (P=0.0056) or PF-4708671 alone (P<0.001) at the end of a 15-day treatment.