SF1126

SF1126 is a clinically relevant pan and dual first-in-class PI3K/BRD4 inhibitor, has antitumor and anti-angiogenic activity. SF1126 is an RGDS-conjugated LY294002 prodrug, which is designed to exhibit increased solubility and bind to specific integrins within the tumor compartment. SF1126 induces cell apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

PI3K/BRD4[1]

SF1126 (0-6 µM; 48 hours) inhibits Hep3B, HepG2, SK-Hep1, and Huh7 cells proliferation with IC50s of 5.05, 6.89, 3.14, and 2.14 µM, respectively[1]. SF1126 (1-10 µM; 24 hours) results in cell-cycle arrest with a proportional increase in G0-G1 and a decrease in the number of cells in the S-phase in Hep 3B, Hep G2, SK-Hep1, and Huh7 cells[1]. SF1126 (0.5-2.5 µM; pre-30 minutes) and sorafenib suggests that combined treatment of SF1126 and sorafenib blocks multiple key enzymes in PI3K/AKT/mTOR and Ras/Raf/MAPK pathway[1]. Cell Viability Assay[1] Cell Line: Hep3B, HepG2, SK-Hep1, and Huh7 cells Concentration: 0 µM; 1 µM; 2 µM; 3 µM; 4 µM; 5 µM; 6 µM Incubation Time: 48 hours Result: Resulted in an increased inhibition of HCC proliferation. Cell Cycle Analysis[1] Cell Line: Hep3B, HepG2, SK-Hep1, and Huh7 cells Concentration: 1 µM; 5 µM; 10 µM Incubation Time: 24 hours Result: Induced cell-cycle arrest. Western Blot Analysis[1] Cell Line: Hep3B, HepG2, SK-Hep1, and Huh7 cells Concentration: 0.5 µM and 2.5 µM Incubation Time: Pre-30 mins Result: Suppressed phosphorylation of AKT, p70S6K, 4EBP1, and ERK in all the cell lines together with sorafenib.

[1]. Garlich JR, et al. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res. 2008 Jan 1;68(1):206-15.