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.
