Buparlisib is a brain penetrable pan-PI3K inhibitor

Area of Science:

• Neuro-oncology
• Pharmacology
• Molecular Biology

Background:

• The PI3K-AKT-mTOR pathway is crucial in brain tumour development.
• Targeting this pathway with phosphatidylinositol 3-kinase (PI3K) inhibitors is a potential therapeutic strategy.
• Effective treatment requires drugs that penetrate the blood-brain barrier.

Purpose of the Study:

• To evaluate the brain penetration of buparlisib, a novel pan-PI3K inhibitor.
• To assess its potential as a therapeutic agent for intracranial tumours.

Main Methods:

• In vitro assays.
• In vivo mouse models.
• Assessment of blood-brain barrier penetration and efflux transporter interactions.
• Evaluation of oral bioavailability and target inhibition.

Main Results:

• Buparlisib demonstrated excellent brain penetration.
• Its penetration was not affected by blood-brain barrier efflux transporters.
• Complete oral bioavailability and efficient intracranial target inhibition were observed at clinically relevant plasma concentrations.

Conclusions:

• Buparlisib possesses ideal characteristics for targeting brain tumours.
• Its properties support its development for PI3K-inhibitor-based therapies against intracranial malignancies.