TY - JOUR T1 - A resource for exploring the understudied human kinome for research and therapeutic opportunities JF - bioRxiv DO - 10.1101/2020.04.02.022277 SP - 2020.04.02.022277 AU - Nienke Moret AU - Changchang Liu AU - Benjamin M. Gyori AU - John A. Bachman AU - Albert Steppi AU - Clemens Hug AU - Rahil Taujale AU - Liang-Chin Huang AU - Matthew E. Berginski AU - Shawn M. Gomez AU - Natarajan Kannan AU - Peter K. Sorger Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/11/2020.04.02.022277.abstract N2 - The functions of protein kinases have been widely studied and over 60 kinase inhibitors are FDA-approved drugs. Membership in the human kinome is nonetheless subject to multiple overlapping and inconsistent definitions and is unevenly studied, complicating functional genomics and chemical genetics. We describe objective criteria for refining the definition of the human kinome to comprise an extended set of 710 kinase domains and a more narrowly curated set of 557 protein kinase like (PKL) domains. An online tool (www.kinome.org) makes it possible to sort these sets on multiple structural and functional criteria. Focusing on the least studied one-third of the kinome we find that many proteins are differentially expressed, essential in multiple cell lines, and mutated in the Cancer Genome Atlas. We show that some understudied kinases are high affinity off-targets of clinical-grade compounds and approved drugs and we describe an optimized small molecule library making use of this information for selective kinome perturbation. We conclude that the understudied kinome contains physiologically important proteins, including possible targets for future drug discovery campaigns.Competing Interest StatementThe authors have declared no competing interest. ER -