Background
API-1 is an inhibitor of Akt that reduces the level of phosphorylated Akt (IC50 = ~0.8 uM in OVCAR3 cells) by binding to Akt and blocking its translocation to the cell membrane. It reduces cell proliferation in various cancer cell lines, induces apoptosis, and, at a dose of 10 mg/kg per day, decreases tumor growth in a mouse xenograft model. API-1 inhibition of Akt leads to proteasomal degradation of the downstream mediator Mcl-1. Likely independent of Akt binding, API-1 inhibits cell growth (IC50s = 2-5 uM) and induces apoptosis in non-small cell lung and head and neck squamous cancer (NSCLC and HNSCC) cell lines with concomitant increases in caspase-3, -8, and -9 cleavage. It reduces the levels of cellular FLICE-inhibitory protein (c-FLIP), an important regulator of apoptosis, through ubiquitin- and proteasome-mediated degradation. It also has a synergistic effect on apoptosis in combination with TRAIL/APO-2L.The information regarding the reduction in phosphorylated Akt levels, IC50 value, translocation, cell proliferation, and xenograft tumor growth was drawn from a paper that has been retracted; however, the information specified in the retraction statement has not been included.
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