PDK1 disruptors and modulators: a patent review

Expert Opin Ther Pat. 2015 May;25(5):513-37. doi: 10.1517/13543776.2015.1014801. Epub 2015 Feb 15.


Introduction: 3-Phosphoinositide-dependent kinase 1 (PDK1) is a master regulator of the AGC protein kinase family and is a critical activator of multiple pro-survival and oncogenic protein kinases, for which it has garnered considerable interest as an oncology drug target.

Areas covered: This manuscript reviews small molecule patent literature disclosures between October 2011 and September 2014 for both PDK1 activators and inhibitors and restates the selective patents published before September 2011. PDK1 modulators are organized according to pharmaceutical company and chemical structural class.

Expert opinion: Many academic institutions and pharmaceutical companies continue to research into the development of small molecules that can function as PDK1 inhibitors or modulators. To date, >50 patent publications on PDK1 disruptors and modulators have been published since the protein was first discovered in 1998. Most of these molecules act as ATP mimetics, forming similar hydrogen bonding patterns to PDK1 as ATP and functioning as hydrophobic pharmacophores. To achieve selectivity in PDK1 inhibition, the discovery of binding pockets structurally distinctive from the ATP site is a challenging but promising strategy.

Keywords: 3-phosphoinositide-dependent kinase 1; 3-phosphoinositide-dependent kinase 1 inhibitors; 3-phosphoinositide-dependent kinase 1 modulators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases / drug effects*
  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Drug Design*
  • Humans
  • Hydrogen Bonding
  • Patents as Topic
  • Protein Kinase Inhibitors / pharmacology*


  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • 3-Phosphoinositide-Dependent Protein Kinases
  • PDPK1 protein, human