Cayman SC-66

Akt activation requires binding of its pleckstrin homology domain (PHD) to membrane-associated phosphatidylinositol-3,4,5-trisphosphate (PIP₃) or phosphatidylinositol-3,4-bisphosphate (PIP₂). 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.

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