3CQU

Crystal Structure of Akt-1 complexed with substrate peptide and inhibitor

Summary for 3CQU

• Entry DOI: 10.2210/pdb3cqu/pdb
• Related: 3CQW
• Descriptor: RAC-alpha serine/threonine-protein kinase, Glycogen synthase kinase-3 beta, N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine, ... (4 entities in total)
• Functional Keywords: kinase, apoptosis, atp-binding, carbohydrate metabolism, cytoplasm, glucose metabolism, glycogen biosynthesis, glycogen metabolism, membrane, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, sugar transport, transferase, translation regulation, transport, alternative splicing, wnt signaling pathway
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P31749 P49841
• Total number of polymer chains: 2
• Total formula weight: 41022.63

Authors

Pandit, J. (deposition date: 2008-04-03, release date: 2008-05-27, Last modification date: 2024-11-20)

Primary citation

Lippa, B.,Pan, G.,Corbett, M.,Li, C.,Kauffman, G.S.,Pandit, J.,Robinson, S.,Wei, L.,Kozina, E.,Marr, E.S.,Borzillo, G.,Knauth, E.,Barbacci-Tobin, E.G.,Vincent, P.,Troutman, M.,Baker, D.,Rajamohan, F.,Kakar, S.,Clark, T.,Morris, J.
Synthesis and structure based optimization of novel Akt inhibitors
Bioorg.Med.Chem.Lett., 18:3359-3363, 2008

PubMed Abstract: Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).

PubMed: 18456494
DOI: 10.1016/j.bmcl.2008.04.034

Experimental method

X-RAY DIFFRACTION (2.2 Å)