Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery.

  title={Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery.},
  author={Jes{\'u}s R Medina and Charles Wesley Blackledge and Dirk A. Heerding and Nino Campobasso and Paris Ward and Jacques Briand and Lois L. Wright and Jeffrey M. Axten},
  journal={ACS medicinal chemistry letters},
  volume={1 8},
Fragment screening of phosphoinositide-dependent kinase-1 (PDK1) in a biochemical kinase assay afforded hits that were characterized and prioritized based on ligand efficiency and binding interactions with PDK1 as determined by NMR. Subsequent crystallography and follow-up screening led to the discovery of aminoindazole 19, a potent leadlike PDK1 inhibitor with high ligand efficiency. Well-defined structure-activity relationships and protein crystallography provide a basis for further… 

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