Beyond PI3Ks: targeting phosphoinositide kinases in disease

  • Nat Rev Drug Discov. 2023 May;22(5):357-386. doi: 10.1038/s41573-022-00582-5.
John E Burke  1  2 ,  Joanna Triscott  3 ,  Brooke M Emerling  4 ,  Gerald R V Hammond  5
Affiliations
  • 1. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada. [email protected].
  • 2. Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada. [email protected].
  • 3. Department of BioMedical Research, University of Bern, Bern, Switzerland.
  • 4. Sanford Burnham Prebys, La Jolla, CA, USA. [email protected].
  • 5. Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. [email protected].
PMID: 36376561 DOI: 10.1038/s41573-022-00582-5
Abstract

Lipid phosphoinositides are master regulators of almost all aspects of a cell's life and death and are generated by the tightly regulated activity of phosphoinositide Kinases. Although extensive efforts have focused on drugging class I phosphoinositide 3-kinases (PI3Ks), recent years have revealed opportunities for targeting almost all phosphoinositide Kinases in human diseases, including Cancer, immunodeficiencies, Viral Infection and Neurodegenerative Disease. This has led to widespread efforts in the clinical development of potent and selective inhibitors of phosphoinositide Kinases. This Review summarizes our current understanding of the molecular basis for the involvement of phosphoinositide Kinases in disease and assesses the preclinical and clinical development of phosphoinositide kinase inhibitors.