Druggable exosites of the human kino-pocketome

  • George Nicola
  • Irina Kufareva
  • Andrey V. Ilatovskiy
  • Ruben AbagyanEmail author


Small molecules binding at any of the multiple regulatory sites on the molecular surface of a protein kinase may stabilize or disrupt the corresponding interaction, leading to consequent modulation of the kinase cellular activity. As such, each of these sites represents a potential drug target. Even targeting sites outside the immediate ATP site, the so-called exosites, may cause desirable biological effects through an allosteric mechanism. Targeting exosites can alleviate adverse effects and toxicity that is common when ATP-site compounds bind promiscuously to many other types of kinases. In this study we have identified, catalogued, and annotated all potentially druggable exosites on the protein kinase domains within the existing structural human kinome. We then priority-ranked these exosites by those most amenable to drug design. In order to identify pockets that are either consistent across the kinome, or unique and specific to a particular structure, we have also implemented a normalized representation of all pockets, and displayed these graphically. Finally, we have built a database and designed a web-based interface for users interested in accessing the 3-dimensional representations of these pockets. We envision this information will assist drug discovery efforts searching for untargeted binding pockets in the human kinome.


Kinase Kinome Pocket Pocketome Exosite Exositome Drugable Druggable Bioinformatics Cheminformatics Drug discovery Protein Target 



This work was funded by NIH 7-R01-GM074832-05 to RA and American Cancer Society Fellowship PF-07-148-01-CDD to GN.

Supplementary material

10822_2019_276_MOESM1_ESM.xlsx (4.7 mb)
Supplementary file1 (XLSX 4841 kb)


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of CaliforniaSan DiegoUSA

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