Selective VPS34 Inhibitors: High Efficiency Design by Profiting from Small Structural Differences

VPS34 has attracted attention in oncology as a target to modulate autophagy. However, the generation of selective VPS34 inhibitors with suitable PK properties has been a difficult task. The discovery of compound 5 provides lessons in hit prioritization and achieving kinase selectivity while maintaining a good in vivo pharmacokinetic profile.