Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372174 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
Abstract
Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3β. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3β mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 μM).
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Authors
Sujeewa Ranatunga, Juan R. Del Valle,