Buparlisib is a brain penetrable pan-PI3K inhibitor

Sci Rep. 2018 Jul 17;8(1):10784. doi: 10.1038/s41598-018-29062-w.


Characterization of the genomic landscapes of intracranial tumours has revealed a clear role for the PI3K-AKT-mTOR pathway in tumorigenesis and tumour maintenance of these malignancies, making phosphatidylinositol 3-kinase (PI3K) inhibition a promising therapeutic strategy for these tumours. Buparlisib is a novel pan-PI3K inhibitor that is currently in clinical development for various cancers, including primary and secondary brain tumours. Importantly however, earlier studies have revealed that sufficient brain penetration is a prerequisite for antitumor efficacy against intracranial tumours. We therefore investigated the brain penetration of buparlisib using a comprehensive set of in vitro and in vivo mouse models. We demonstrate that buparlisib has an excellent brain penetration that is unaffected by efflux transporters at the blood-brain barrier, complete oral bioavailability and efficient intracranial target inhibition at clinically achievable plasma concentrations. Together, these characteristics make buparlisib the ideal candidate for intracranially-targeted therapeutic strategies that involve PI3K inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aminopyridines / administration & dosage
  • Aminopyridines / pharmacokinetics*
  • Animals
  • Blood-Brain Barrier
  • Brain / metabolism*
  • Female
  • Male
  • Mice
  • Morpholines / administration & dosage
  • Morpholines / pharmacokinetics*
  • Phosphoinositide-3 Kinase Inhibitors*


  • Aminopyridines
  • Morpholines
  • NVP-BKM120
  • Phosphoinositide-3 Kinase Inhibitors