Structure-based design of PDK1 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 1, 2012, Pages 305-307

  Poulsen, Anders ^a   Blanchard, Stéphanie ^a   Soh, Chang Kai ^a   Lee, Chaiping ^a   Williams, Meredith ^a   Wang, Haishan ^a   Dymock, Brian ^a  

^a S BIO Pte Ltd   (Singapore)

Author keywords

3 Phosphoinositide dependent kinase 1 (PDK1); 4 Aryl purine; Inhibitor; Selectivity; Structure based design

Indexed keywords

AMIDE; AMINO ACID; AROMATIC COMPOUND; JANUS KINASE 2 INHIBITOR; MACROCYCLIC COMPOUND; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1 INHIBITOR; PHOSPHOTRANSFERASE; PROTEIN SERINE THREONINE KINASE INHIBITOR; PURINE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; ENZYME ACTIVITY; ENZYME BINDING; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DOCKING; SOLUBILITY; X RAY;

ANIMALS; BINDING SITES; BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; CHEMISTRY, PHYSICAL; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; GENE DELETION; HUMANS; HYDROGEN BONDING; INHIBITORY CONCENTRATION 50; LIGANDS; MICE; MICROSOMES, LIVER; MODELS, CHEMICAL; MOLECULAR CONFORMATION; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PYRIMIDINES; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84655161329     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.11.006     Document Type: Article

References (11)

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11. All computational chemistry software used is from Schrödinger (http://www.schrodinger.com). The PDK1 and CDK2 X-ray structures (1Z5M respectively 1AQ1) were downloaded from the Protein Data Bank (http://www.pdb.org) and prepared with the Protein Preparation Wizard as recommended by Schrodinger. Ligands were prepared with Ligprep and docked into the protein structures using Glide and the XP scoring function with standard settings.