Description
Akt activation requires binding of its pleckstrin homology domain (PHD) to membrane-
associated phosphatidylinositol-
3,4,5-
trisphosphate (PIP
3) or phosphatidylinositol-
3,4-
bisphosphate (PIP
2). Increased Akt activity,
e.g., through a gain-
of-
function mutation in the PHD of Akt1, is pivotal to many types of cancer. Activated Akt may be regulated by various events, including ubiquitination-
mediated deactivation. SC-
66 is an allosteric inhibitor of Akt that facilitates both ubiquitination and deactivation of Akt. At 4 μg/ml, SC-
66 inhibits Akt activity in HEK293T cells and in HEK293 cells stably expressing Akt with the gain-
of-
function pleckstrin homology domain mutation, promoting cell death. In nude mice inoculated with HEK293T cells, SC-
66 (15 mg/kg) suppresses tumor growth.
References
[1] HAKRYUL JO. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 16: 6486-6491. DOI:
10.1073/pnas.1019062108
