Akt Inhibitor XVIII, SC66

A cell-permeable pyridine compound that represses Akt activation by allosterically disrupting Akt-PH domain binding to PIP₃ and directly facilitating Akt ubiquitination with little proteasomal or deubiquitination activity. Blocks phosphorylations of Akt-Ser⁴⁷³ and downstream targets TSC, FOXO and PRAS40 in HEK293T cells at 8 µg/ml with minimal effect on pAkt-Thr⁴⁵⁰. Shown to be highly efficacious towards PI 3-K inhibitor resistant Akt1-E17K mutant and exert synergistic apoptotic activity with LY 294002 (Cat. No. 440202) against HeLa cells. Suppresses tumor growth in a mouse HEK293T-xenograft model (30 mg/kg, s.c., twice per week).

A cell-permeable pyridine compound that selectively targets Akt, but not PLCδ, PH domain, preventing Akt membrane localization/activation and rendering Akt in a conformation susceptible to ubiquitination and subsequent proteasomal degradation. Akti-1/2 (Cat. Nos. 124017 & 124018) competes for Akt PH domain binding and blocks SC66-induced Akt ubiquitination and proteasomal degradation. Effectively inhibits HEK293T growth both in vitro (>99 inhibition at 0.4 M) and in mice in vivo (84% of control tumor size with twice weekly i.p. dose of 30 mg/kg), Synergizes with LY294002 (Cat. Nos. 440202 & 440204) in cell death induction in HeLa and HS-Sultan cultures in vitro.

Toxicity: Regulatory Review (Z)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 1 month at -20°C.

Jo, H., et al. 2011. Proc. Natl. Acad. Sci. USA108, 6486.

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