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PF-4708671

CAS No. : 1255517-76-0

MCE 国际站：PF-4708671

产品活性：PF-4708671 是一种有效的细胞渗透性 S6K1 抑制剂，K_i 为 20 nM，IC₅₀ 为 160 nM。

研究领域：MAPK/ERK Pathway  |  Autophagy

作用靶点：Ribosomal S6 Kinase (RSK)  |  Autophagy

In Vitro: PF-4708671 inhibits the activity of full-length S6K1 in vitro with a K_i 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.

In Vivo: 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.

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