Allosteric Small-Molecule Serine/Threonine Kinase Inhibitors

  • Resmi C. Panicker
  • Souvik Chattopadhaya
  • Anthony G. Coyne
  • Rajavel SrinivasanEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1163)


Deregulation of protein kinase activity has been linked to many diseases ranging from cancer to AIDS and neurodegenerative diseases. Not surprisingly, drugging the human kinome – the complete set of kinases encoded by the human genome – has been one of the major drug discovery pipelines. Majority of the approved clinical kinase inhibitors target the ATP binding site of kinases. However, the remarkable sequence and structural similarity of ATP binding pockets of kinases make selective inhibition of kinases a daunting task. To circumvent these issues, allosteric inhibitors that target sites other than the orthosteric ATP binding pocket have been developed. The structural diversity of the allosteric sites allows these inhibitors to have higher selectivity, lower toxicity and improved physiochemical properties and overcome drug resistance associated with the use of conventional kinase inhibitors. In this chapter, we will focus on the allosteric inhibitors of selected serine/threonine kinases, outline the benefits of using these inhibitors and discuss the challenges and future opportunities.


Kinase allostery Allosteric inhibitors SMKI FBDD MEK allosteric inhibitors Aurora A kinase Aurora A-TPX2 CK2α CDK Akt 



RS acknowledges the School of Pharmaceutical Science and Technology (SPST), Tianjin University for the funding support and Tianjin municipal government for the Tianjin 1000-Talents (Youth) award. RCP acknowledges the Tianjin University for the Post-Doctoral Fellowship support.


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Resmi C. Panicker
    • 1
  • Souvik Chattopadhaya
    • 2
  • Anthony G. Coyne
    • 3
  • Rajavel Srinivasan
    • 1
    Email author
  1. 1.School of Pharmaceutical Science and TechnologyTianjin UniversityTianjinPeople’s Republic of China
  2. 2.School of Applied SciencesRepublic PolytechnicSingaporeSingapore
  3. 3.University Chemical LaboratoryUniversity of CambridgeCambridgeUK

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