API-1

API-1 is an inhibitor of Akt that reduces the level of phosphorylated Akt (IC₅₀ = ~0.8 µM in OVCAR3 cells) by binding to Akt and blocking its translocation to the cell membrane.¹ 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-1.² Likely independent of Akt binding, API-1 inhibits cell growth (IC₅₀s = 2-5 µM) 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.³ 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Akt levels, IC₅₀ value, translocation, cell proliferation, and xenograft tumor growth was drawn from a paper that has been retracted; however, the information specified in the retraction statement has not been included.¹

WARNING This product is not for human or veterinary use.

1. Kim, D., Sun, M., He, L., et al. A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation. The Journal of Biological Chemisty 285(11), 8383-8394 (2010).

2. Ren, H., Koo, J., Guan, B., et al. The E₃ ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis. Mol. Cancer 12, 146 (2013).

3. Li, B., Ren, H., Yue, P., et al. The novel Akt inhibitor API-1 induces c-FLIP degradation and synergizes with TRAIL to augment apoptosis independent of Akt inhibition. Cancer Prev. Res. (Phila.) 5(4), 612-620 (2012).