3IOP

PDK-1 in complex with the inhibitor Compound-8i

Summary for 3IOP

• Entry DOI: 10.2210/pdb3iop/pdb
• Related: 3ION
• Descriptor: 3-phosphoinositide-dependent protein kinase 1, 2-(5-{[(2R)-2-amino-3-phenylpropyl]oxy}pyridin-3-yl)-8,9-dimethoxybenzo[c][2,7]naphthyridin-4-amine (3 entities in total)
• Functional Keywords: pdk-1, inhibitor, alternative splicing, atp-binding, cytoplasm, kinase, membrane, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O15530
• Total number of polymer chains: 1
• Total formula weight: 36134.40

Authors

Olland, A.M. (deposition date: 2009-08-14, release date: 2010-02-16, Last modification date: 2024-10-16)

Primary citation

Nittoli, T.,Dushin, R.G.,Ingalls, C.,Cheung, K.,Floyd, M.B.,Fraser, H.,Olland, A.,Hu, Y.,Grosu, G.,Han, X.,Arndt, K.,Guo, B.,Wissner, A.
The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1).
Eur.J.Med.Chem., 45:1379-1386, 2010

PubMed Abstract: A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer.

PubMed: 20074837
DOI: 10.1016/j.ejmech.2009.12.036

Experimental method

X-RAY DIFFRACTION (2.2 Å)