PF-4708671

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-4708671 是一种 p70 核糖体 S6 激酶（S6K1 亚型）的细胞渗透性抑制剂，在无细胞测定中 Ki/IC50 为 20 nM/160 nM。

PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. First S6K1-specific inhibitor to be reported.

PF-4708671 inhibits the activity of full-length S6K1 in vitro with a Ki of 20 nM, and S6K1 isolated from IGF1-stimulated HEK293 cells with an IC50 of 0.16 μM, and only inhibits very weakly the closely related S6K2 isoform (IC50 of 65 μM). PF-4708671 inhibits RSK1 (IC50 of 4.7 μM) and RSK2 (IC50 of 9.2 μM) over 20-fold less potently than S6K1. PF4708671 inhibits MSK1 (IC50 of 0.95 μM) 4-fold more weakly than S6K1. HCT116 cells are treated with (i) vehicle (DMSO), (ii) OSI-906 (5 μM), (iii) PF-4708671 (10 μM), and (iv) OSI-906 (5 μM)+PF-4708671 (10 μM) for various amounts of time. HCT116 cells treated with OSI-906 alone (closed square) or PF4708671 alone (open circle) slightly inhibit cell growth. In contrast, proliferation in HCT116 cells is significantly inhibited after a 2-day treatment with the combination of OSI-906 and PF-4708671 (closed circle). A similar result is also observed when SW480 cells are treated with the combination of OSI-906 and PF-4708671. Colony formation also significantly reduces in OSI-906+PF-4708671-treated cells comparing with vehicle, OSI-906 alone, or PF-4708671 alone treated HCT116 or SW480 cells.

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.

PF4708671 | PF-4708671 | PF 4708671

PI3K/Akt/mTOR signaling

S6 Kinase

p70 S6K

Cancer

——

1255517-76-0

390.41

C19H21F3N6

>98% (HPLC)

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

FC(C1=CC=C2NC(CN3CCN(C4=NC=NC=C4CC)CC3)=NC2=C1)(F)F

2-((4-(5-ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-5-(trifluoromethyl)-1H-benzo[d]imidazole

(-20℃)

With Ice Pack

≥ 2 years