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Discovery of a novel protein kinase B inhibitor by structure-based virtual screening |
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| Authors: | Jose L. Medina-Franco Marc A. Giulianotti Yongping Yu Liangliang Shen Libo Yao Narender Singh |
| Affiliation: | 1. Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA;2. College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China;3. Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China |
| Abstract: | Protein kinase B (PKB/AKT) is a promising and attractive therapeutic target in anticancer drug development. Herein, we report the findings of virtual screening for novel ATP-competitive inhibitors of AKT-2 using 2D- and 3D-similarity searching and sequential molecular docking with two crystal structures of AKT-2. Our multistep approach led to the identification of a low micromolar AKT-2 inhibitor (IC50 = 1.5 μM) with a novel scaffold. The experimentally validated inhibitor represents the starting point for an optimization program. |
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